elastin and Connective-Tissue-Diseases

Elastic fibers are essential assemblies of vertebrates and confer elasticity and resilience to various organs including blood vessels, lungs, skin, and ligaments. Mature fibers, which comprise a dense and insoluble elastin core and a microfibrillar mantle, are extremely resistant toward intrinsic and extrinsic influences and maintain elastic function over the human lifespan in healthy conditions. The oxidative deamination of peptidyl lysine to peptidyl allysine in elastin's precursor tropoelastin is a crucial posttranslational step in their formation. The modification is catalyzed by members of the family of lysyl oxidases and the starting point for subsequent manifold condensation reactions that eventually lead to the highly cross-linked elastomer. This review summarizes the current understanding of the formation of cross-links within and between the monomer molecules, the molecular sites, and cross-link types involved and the pathological consequences of abnormalities in the cross-linking process.

Topics: 2-Aminoadipic Acid; Aging; Animals; Blood Vessels; Connective Tissue Diseases; Elastic Tissue; Elastin; Humans; Ligaments; Lung; Lysine; Microfibrils; Oxidation-Reduction; Protein Processing, Post-Translational; Protein-Lysine 6-Oxidase; Skin

Lysyl oxidase like 3 (LOXL3) is a copper-dependent amine oxidase responsible for the crosslinking of collagen and elastin in the extracellular matrix. LOXL3 belongs to a family including other members: LOX, LOXL1, LOXL2, and LOXL4. Autosomal recessive mutations are rare and described in patients with Stickler syndrome, early-onset myopia and non-syndromic cleft palate. Along with an essential function in embryonic development, multiple biological functions have been attributed to LOXL3 in various pathologies related to amino oxidase activity. Additionally, various novel roles have been described for LOXL3, such as the oxidation of fibronectin in myotendinous junction formation, and of deacetylation and deacetylimination activities of STAT3 to control of inflammatory response. In tumors, three distinct roles were described: (1) LOXL3 interacts with SNAIL and contributes to proliferation and metastasis by inducing epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma cells; (2) LOXL3 is localized predominantly in the nucleus associated with invasion and poor gastric cancer prognosis; (3) LOXL3 interacts with proteins involved in DNA stability and mitosis completion, contributing to melanoma progression and sustained proliferation. Here we review the structure, function and activity of LOXL3 in normal and pathological conditions and discuss the potential of LOXL3 as a therapeutic target in various diseases.

Topics: Amino Acid Oxidoreductases; Arthritis; Cleft Palate; Collagen; Connective Tissue Diseases; Elastin; Epithelial-Mesenchymal Transition; Extracellular Matrix; Gene Expression Regulation; Hearing Loss, Sensorineural; Humans; Isoenzymes; Myopia; Neoplasms; Organ Specificity; Retinal Detachment; Signal Transduction; Snail Family Transcription Factors; STAT3 Transcription Factor

Human elastases have been identified within serine, cysteine and metallopeptidase families. These enzymes are able to adsorb rapidly onto elastin, but they can also bind onto cell surface-associated proteins such as heparan sulfate proteoglycans, both interactions involving enzyme exosites distinct form active site. Immobilization of elastin at the cell surface will create a sequestered microenvironment and will favour elastolysis. Generated elastin peptides are potent matrikines displaying dual biological functions in physiopathology that are described in this review. Among properties, they are potent inducers of protease expression catalyzing collagenolysis or amplifying elastin degradation. The ability of unsaturated fatty acids and heparin(s) to control elastases action are delineated.

Topics: Adsorption; Animals; Connective Tissue Diseases; Cysteine Endopeptidases; Elastic Tissue; Elastin; Fatty Acids, Unsaturated; Humans; Leukocyte Elastase; Macrophages; Metalloendopeptidases; Neutrophils; Pancreatic Elastase; Receptors, Cell Surface; Serine Endopeptidases

Abdominal aortic aneurysms (AAAs) and abdominal wall hernias represent chronic degenerative conditions. Both aortic aneurysms and inguinal hernias share common epidemiologic features, and several investigators have found an increased propensity for hernia development in patients treated for aortic aneurysms. Chronic inflammation and dysregulation in connective tissue metabolism constitute underlying biological processes, whereas genetic influences appear to be independently associated with both disease states. A literature review was conducted to identify all published evidence correlating aneurysms and hernias to a common pathology.. PubMed/Medline was searched for studies investigating the clinical, biochemical, and genetic associations of AAAs and abdominal wall hernias. The literature was searched using the MeSH terms "aortic aneurysm, abdominal," "hernia, inguinal," "hernia, ventral," "collagen," "connective tissue," "matrix metalloproteinases," and "genetics" in all possible combinations. An evaluation, analysis, and critical overview of current clinical data and pathogenic mechanisms suggesting an association between aneurysms and hernias were undertaken.. Ample evidence lending support to the clinical correlation between AAAs and abdominal wall hernias exists. Pooled analysis demonstrated that patients undergoing aortic aneurysm repair through a midline abdominal incision have a 2.9-fold increased risk of developing a postoperative incisional hernia compared with patients treated for aortoiliac occlusive disease (odds ratio, 2.86; 95% confidence interval, 1.97-4.16; P < .00001), whereas the risk of inguinal hernia was 2.3 (odds ratio, 2.30; 95% confidence interval, 1.52-3.48; P < .0001). Emerging evidence has identified inguinal hernia as an independent risk factor for aneurysm development. Although mechanisms of extracellular matrix remodeling and the imbalance between connective tissue degrading enzymes and their inhibitors instigating inflammatory responses have separately been described for both disease states, comparative studies investigating these biological processes in aneurysm and hernia populations are scarce. A genetic predisposition has been documented in familial and observational segregation studies; however, the pertinent literature lacks sufficient supporting evidence for a common genetic basis for aneurysm and hernia.. Insufficient data are currently available to support a systemic connective tissue defect affecting the structural integrity of the aortic and abdominal wall. Future investigations may elucidate obscure aspects of aneurysm and hernia pathophysiology and create novel targets for pharmaceutical and gene strategies for disease prevention and treatment.

Topics: Aortic Aneurysm, Abdominal; Collagen; Connective Tissue Diseases; Elastin; Genetic Predisposition to Disease; Hernia, Abdominal; Hernia, Inguinal; Humans; Matrix Metalloproteinases; Odds Ratio; Risk Assessment; Risk Factors; Vascular Surgical Procedures

Elastic fibres are a major class of extracellular matrix fibres that are abundant in dynamic connective tissues such as arteries, lungs, skin and ligaments. Their structural role is to endow tissues with elastic recoil and resilience. They also act as an important adhesion template for cells, and they regulate growth factor availability. Mutations in major structural components of elastic fibres, especially elastin, fibrillins and fibulin-5, cause severe, often life-threatening, heritable connective tissue diseases such as Marfan syndrome, supravalvular aortic stenosis and cutis laxa. Elastic-fibre function is also frequently compromised in damaged or aged elastic tissues. The ability to regenerate or engineer elastic fibres and tissues remains a significant challenge, requiring improved understanding of the molecular and cellular basis of elastic-fibre biology and pathology, and ability to regulate the spatiotemporal expression and assembly of its molecular components.

Topics: Animals; Aortic Stenosis, Supravalvular; Connective Tissue; Connective Tissue Diseases; Elastic Tissue; Elastin; Extracellular Matrix; Extracellular Matrix Proteins; Fibrillins; Humans; Marfan Syndrome; Mice; Microfilament Proteins; Models, Biological; Recombinant Proteins; Time Factors; Tissue Distribution

Elastic fibers in the extracellular matrix are an integral component of dermal connective tissue. The resilience and elasticity required for normal structure and function of the skin may be attributed to the network of elastic tissue. Advances in our understanding of elastic tissue physiology provide a foundation for studying the pathogenesis of elastic tissue disorders. Many acquired disorders are nevertheless poorly understood due to the paucity of reported cases. Several acquired disorders in which accumulation or elastotic degeneration of dermal elastic fibers produces prominent clinical and histopathologic features have recently been described. They include elastoderma, linear focal elastosis, and late-onset focal dermal elastosis and must be differentiated from better-known disorders, among them acquired pseudoxanthoma elasticum, elastosis perforans serpiginosa, and Favré-Racouchot syndrome. Learning objective At the conclusion of this learning activity, participants should understand the similarities and differences between acquired disorders of elastic tissue that are characterized by an increase in elastic tissue, as well as the spectrum of solar elastotic dermatoses.

Topics: Connective Tissue Diseases; Diagnosis, Differential; Elastic Tissue; Elasticity; Elastin; Humans; Pseudoxanthoma Elasticum

Topics: Connective Tissue Diseases; Elastic Tissue; Elastin; Extracellular Matrix Proteins; Fibrillins; Humans; Microfibrils; Microfilament Proteins; Mutation

Over the last decade, a considerable amount of new information has emerged describing the protein components of elastic fibers. It is now evident that elastic fibers are complex extracellular matrix polymers, composed of at least 19 different proteins that comprise both the microfibrillar and the amorphous components of elastic fibers. Mutations in three of the genes encoding the most abundant of these elastic fiber proteins result in a broad spectrum of elastic tissue phenotypes, ranging from skeletal and skin abnormalities to vascular and ocular defects. The following disorders will be discussed in this review: supravalvular aortic stenosis; Williams-Beuren syndrome; cutis laxa; Marfan syndrome; ectopia lentis; familial thoracic aortic aneurysms and dissections; MASS syndrome; isolated skeletal features of Marfan syndrome; Shprintzen-Goldberg syndrome; and congenital contractural arachnodactyly.

Topics: Aortic Stenosis, Supravalvular; Connective Tissue Diseases; Cutis Laxa; Elastic Tissue; Elastin; Extracellular Matrix Proteins; Fibrillins; Humans; Marfan Syndrome; Microfilament Proteins; Mutation; Phenotype

The inability to study appropriate human tissues at various stages of development has precluded the elaboration of a thorough understanding of the pathogenic mechanisms leading to diseases linked to mutations in genes for elastic fiber proteins. Recently, new insights have been gained by studying mice harboring targeted mutations in the genes that encode fibrillin-1 and elastin. These genes have been linked to Marfan syndrome (MFS) and supravalvular aortic stenosis (SVAS), respectively. For fibrillin-1, mouse models have revealed that phenotype is determined by the degree of functional impairment. The haploinsufficiency state or the expression of low levels of a product with dominant-negative potential from one allele is associated with mild phenotypes with a predominance of skeletal features. Exuberant expression of a dominant-negative-acting protein leads to the more severe MFS phenotype. Mice harboring targeted deletion of the elastin gene (ELN) show many of the features of SVAS in humans, including abnormalities in the vascular wall and altered hemodynamics associated with changes in wall compliance. The genetically altered mice suggest that SVAS is predominantly a disease of haploinsufficiency. These studies have underscored the prominent role of the elastic matrix in the morphogenesis and homeostasis of the vessel wall.

Topics: Animals; Aortic Stenosis, Supravalvular; Connective Tissue Diseases; Disease Models, Animal; Elastin; Extracellular Matrix Proteins; Fibrillin-1; Fibrillins; Humans; Marfan Syndrome; Mice; Microfilament Proteins; Models, Genetic; Mutation

Topics: Actin Cytoskeleton; Amino Acid Sequence; Connective Tissue; Connective Tissue Diseases; Elastin; Extracellular Matrix Proteins; Fibrillins; Humans; Marfan Syndrome; Microfilament Proteins; Molecular Sequence Data; Sequence Homology, Amino Acid

Topics: Chromosome Mapping; Connective Tissue Diseases; DNA; DNA, Recombinant; Elastin; Gene Expression Regulation; Humans; Polymorphism, Genetic

A skin biopsy contains the macromolecules present in most connective tissues: collagens, elastin, glycoproteins, and proteoglycans. The specific combination and assembly of these matrix components and their interactions with other structures (e.g., epidermal appendages, nerve and vascular networks) and cells are responsible for the distinction among specific regions of the dermis. The matrix components are interactive and interdependent and modification of one of them, by extrinsic (environmental) and/or intrinsic (systemic, genetic, age-related) factors, may have consequences on the tissue as a whole. The skin, therefore, provides a window through which it is possible to examine how mutations in one connective tissue macromolecule can change the interactions among matrix components and affect tissue structure and organization. Light and electron microscopic studies of skin from patients with inherited connective tissue disorders (e.g., Ehlers-Danlos syndrome, osteogenesis imperfecta, Marfan syndrome, cutis laxa) have led us to the following generalizations about what components change, how individual collagen or elastic fibers are altered and how individual alterations affect overall dermal organization: 1) There is a limited change in the repertoire of collagen fibrils in the skin; 2) there appears to be a greater range of abnormal structure in dermal elastic fibers than in the collagen fibrils; 3) the morphology of the fibroblastic cells may provide clues to the defect in matrix components; 4) similar structural abnormalities result from different molecular defect; 5) a molecular defect in one connective tissue molecule has consequences for the structural properties of other connective tissue components; and 6) although structural alterations in connective tissue fibers are rarely specific for a given disease, there are characteristic patterns of structural change in the matrix that may be used to confirm a diagnosis. These generalizations show that mutations rarely affect only a single aspect of macromolecular function and because of the interactions of matrix components in this complex organ (skin) often disturb the organization of the entire dermis. Genotype-phenotype relationships are important to understand if effective therapies are to be designed. The structure of skin should provide the next level of integration in our efforts to determine how mutations produce disease.

Topics: Collagen; Connective Tissue Diseases; Elastin; Fibroblasts; Humans; Mutation; Skin

Topics: Animals; Biomechanical Phenomena; Chemical Phenomena; Chemistry; Collagen; Connective Tissue Diseases; Elastin; Humans; Mutation

Aging of human skin represents a complex situation where several factors contribute to the age-related changes. One of these factors relates to UV-radiation, but the exact mechanistic details are not well established. Several morphologic studies have indicated definite changes in the quantitative aspects of dermal connective tissue components, collagen and elastin. Also, recent biochemical studies have suggested that UV-irradiation can alter the metabolism of these proteins in the skin. This review summarizes the current state of knowledge of the effects of natural and therapeutic UV-radiation on dermal connective tissue, and further delineates additional research needs necessary for disclosure of the exact mechanistic details of the aging processes in human skin.

Topics: Animals; Collagen; Connective Tissue; Connective Tissue Diseases; Disease Models, Animal; Elastin; Fibroblasts; Humans; Mice; Photochemotherapy; PUVA Therapy; Skin; Ultraviolet Rays

Topics: 2-Aminoadipic Acid; Animals; Basement Membrane; Cells, Cultured; Chemical Phenomena; Chemistry; Collagen; Connective Tissue Diseases; Cross-Linking Reagents; Elastin; Histidine; Humans; Metabolism, Inborn Errors; Models, Molecular; Protein-Lysine 6-Oxidase; Pyridines; Rats

Topics: Animals; Chemotaxis; Collagen; Connective Tissue; Connective Tissue Diseases; Elastin; Fibronectins; Humans; Lung; Phagocytosis; Pneumonia; Proteoglycans; Pulmonary Emphysema; Pulmonary Fibrosis

Topics: Collagen; Connective Tissue Diseases; Cutis Laxa; Ehlers-Danlos Syndrome; Elastin; Fibronectins; Humans; Marfan Syndrome; Metabolism, Inborn Errors; Osteogenesis Imperfecta; Prenatal Diagnosis; Proteoglycans; Skin

Stretch marks are disfiguring lesions usually caused by excessive stretching of skin. We investigated the response of early, clinically active stretch marks to topical 0.1% tretinoin (retinoic acid) cream. In a double-blind, randomized, vehicle-controlled study, 22 patients applied either 0.1% tretinoin (n = 10) or vehicle (n = 12) daily for 6 months to the affected areas. Patients were evaluated by physical examination monthly and by analysis of biopsy specimens of stretch marks obtained before and at the end of therapy in comparison with untreated normal skin.. After 2 months, patients treated with tretinoin had significant improvements in severity scores of stretch marks compared with patients who received vehicle (P < .05). After 6 months, eight (80%) of the 10 tretinoin-treated patients had definite or marked improvement compared with one (8%) of the 12 vehicle-treated patients (P = .002). Targeted stretch marks in patients treated with tretinoin had a decrease in mean length and width of 14% and 8%, respectively, compared with an increase of 10% (P < .001) and 24% (P = .008), respectively, in patients who received vehicle. There were no significant differences in various measures of quality and quantity of dermal collagen and elastic fibers in stretch marks when tretinoin and vehicle treatments were compared.. Topical application of tretinoin significantly improves the clinical appearance of early, active stretch marks. The processes that are responsible for the clinical improvement remain unknown.

Topics: Administration, Cutaneous; Adult; Collagen; Connective Tissue Diseases; Desmosine; Double-Blind Method; Elastin; Female; Humans; Keratolytic Agents; Male; Skin; Surveys and Questionnaires; Time Factors; Treatment Outcome; Tretinoin

Fragile X syndrome (FXS) is an inherited genetic condition that is the leading known cause of inherited intellectual developmental disability. Phenotypically, individuals with FXS also present with distinct physical features including, elongated face, prominent ears, pectus excavatum, macroorchidism, and joint laxity, which suggests connective tissue dysplasia. In addition to mitral valve prolapse, aortic dilatation has been identified within individuals with FXS. Abnormal elastin fiber networks have been found in the skin, valves, and aorta in individual cases. Aortic dilatation has been described in other connective tissue disorders, particularly Marfan syndrome. However, while aortic aneurysms are characteristic of Marfan syndrome, no similar cases have been reported in FXS patients to date. This case report details the presentation of two patients with FXS and aortic aneurysm. Our two cases highlight the risks of aortic pathology in FXS, and the need for monitoring in asymptomatic patients with significant aortic dilatation.

Topics: Aortic Aneurysm; Connective Tissue Diseases; Elastin; Fragile X Syndrome; Humans; Marfan Syndrome; Mitral Valve Prolapse

Topics: Adult; Connective Tissue Diseases; Diagnosis, Differential; Elastic Tissue; Elastin; Female; Folliculitis; Humans; Lupus Nephritis

Costello syndrome is a connective tissue disorder associated with sparse, thin, and fragmented elastic fibers in tissues. In this study we demonstrated a significant decrease in the expression of tropoelastin mRNA in fibroblasts derived from a Japanese Costello syndrome patient with impaired elastogenesis and enhanced proliferation. In contrast, there were no changes in expression of the Harvey ras (HRAS), fibrillin-1, fibulin-5, microfibril-associated glycoprotein-1 (MAGP-1), lysyl oxidase (LOX), or 67-kDa non-integrin elastin-binding protein (EBP) gene. The proliferative activity of the Costello fibroblasts was about 4-fold higher than that of the normal and pathological control ones. However, no mutations were detected in the coding region of HRAS mRNA. Transduction of the bovine tropoelastin (bTE) gene with the lentiviral vector restored the elastic fiber formation and decreased the growth rate in the Costello fibroblasts. These results strongly suggest that the defect of human tropoelastin (hTE) gene expression should induce the impaired elastogenesis and enhanced proliferation of Costello fibroblasts, and that a primary cause other than the HRAS gene mutation should contribute to the pathogenesis in the present Costello case.

Topics: Abnormalities, Multiple; Adolescent; Animals; Asian People; Cattle; Cell Proliferation; Connective Tissue Diseases; DNA, Complementary; Elastin; Female; Fibroblasts; Gene Expression Regulation; Humans; RNA, Messenger; Skin; Transduction, Genetic; Tropoelastin

A 12-year-old girl with trisomy 21 (Downs syndrome) presented with an approximate 2-year history of an asymptomatic eruption on the right upper arm and left lateral neck that was clinically and histologically diagnostic of elastosis perforans serpiginosa (EPS). EPS is a perforating dermatosis affecting the face, ear, neck, extremities, or trunk. It occurs with greater frequency in persons with trisomy 21, as well as some other genetic syndromes and after D-penicillamine therapy. It has also been reported as a sporadic, presumably unrelated disorder in several acquired diseases.

Topics: Child; Connective Tissue Diseases; Down Syndrome; Elastic Tissue; Elastin; Female; Humans; Skin Diseases

Topics: Angiography; Biopsy; Carotid Artery, Internal, Dissection; Causality; Cerebral Infarction; Connective Tissue; Connective Tissue Diseases; Elastin; Humans; Male; Middle Aged; Recurrence; Skin Diseases; Vertebral Artery Dissection

Fibulin-5 was recently found as a secreted extracellular matrix protein that functions as a scaffold for elastic fibres. However, the distribution of fibulin-5 in human skin and its changes during the ageing process are not known.. To explore the involvement of fibulin-5 in skin ageing, the age-dependent changes in fibulin-5 localization in human skin were examined compared with those of other elastic fibre components including elastin, fibrillin-1 and fibulin-2. Methods The distribution of elastin, fibrillin-1, fibrillin-2, fibulin-2 and fibulin-5 was investigated by means of immunohistochemistry using their specific antibodies. Skin samples were recovered from 12 healthy subjects undergoing plastic surgery. Ultraviolet (UV) B-irradiated or control nonirradiated buttock skin samples were obtained from two healthy volunteers at 2 days after the irradiation at 2 minimal erythemal doses.. In the reticular dermis of young sun-protected skin from the upper arm, fibulin-5 colocalized with the other elastic fibre components, while in the papillary dermis fibulin-5 showed candelabra-like structures perpendicular to the epidermis with an unstained area just beneath the epidermis, which was similar to that of elastin but not fibrillin-1. Fibulin-5 in the reticular dermis decreased and disappeared with age even in sun-protected skin from the thigh, abdomen and upper arm. In sun-exposed skin, fibulin-5 was extremely reduced in the dermis of cheek skin even from a 20-year-old man. UVB irradiation reduced fibulin-5, fibulin-2 and elastin markedly, moderately and weakly, respectively, compared with levels in control nontreated skin. Interestingly, the deposition of fibulin-5 was increased in solar elastosis, like that of other elastic fibre components.. These results suggest that fibulin-5 is a good marker of skin ageing and that the earlier loss of fibulin-5 may involve age-dependent changes in other elastic fibre components.

Topics: Adolescent; Adult; Aged; Biomarkers; Calcium-Binding Proteins; Child; Child, Preschool; Connective Tissue Diseases; Dermis; Elastin; Extracellular Matrix Proteins; Female; Fibrillin-1; Fibrillin-2; Fibrillins; Humans; Immunohistochemistry; Male; Microfilament Proteins; Middle Aged; Recombinant Proteins; Skin Aging; Ultraviolet Rays

A method is described that could be of potential use for the rapid ultrastructural identification of abnormal and fragmented elastic fibers in very small wet samples of dermal biopsies from patients affected by Pseudoxanthoma elasticum (PXE). Moreover, the method, which consists of the use of sealed capsules transparent to electrons, allows the rapid and accurate localization and detection of mineralized areas in PXE patients and of their ion composition by X-ray microanalysis. This methodology could be of great help in any tissue disorder, especially in connective tissue disorders, characterized by structural alterations associated with ion precipitation.

Topics: Biopsy; Calcinosis; Connective Tissue Diseases; Elastic Tissue; Elastin; Electron Probe Microanalysis; Humans; Ions; Pseudoxanthoma Elasticum; Skin

Antibodies (Abs) to alpha-elastin (elastin breakdown product) and tropoelastin (elastin precursor) are found in the serum of all human subjects and correlate with their respective serum peptide levels; however, peptide levels vary with age and some disease states. This study was undertaken to determine if serum elastin Abs, peptides, and elastin metabolism were altered in autoimmune diseases by detecting a changing ratio of serum anti-alpha:tropoelastin Ab levels.. Serum from patients with a variety of connective tissue diseases, including 28 with systemic lupus erythematosus (SLE), 24 with scleroderma, 18 with rheumatoid arthritis (RA), 10 with polymyositis, and 39 with vasculitis, was compared with serum from 19 age-matched healthy subjects for levels of antitropoelastin and anti-alpha-elastin Abs.. We found an increase in IgG anti-alpha-elastin and a decrease in antitropoelastin Abs in the sera of patients with scleroderma (p < .02 and .00005) and SLE (p < .006 and .011). There was also a marked increase in anti-alpha-elastin Abs in patients with polyarteritis nodosa (p < .0005) and decreases in antitropoelastin Abs in patients with RA (p < .05), polymyositis (p < .01), and a variety of other vasculidities (p < .0003).. Abnormal variations in elastin metabolism may be detected in several connective tissue diseases by measuring ratios of alpha- and tropoelastin IgG Abs as markers of elastin degradation and synthesis.

Topics: Adolescent; Adult; Antibodies; Connective Tissue Diseases; Cross Reactions; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin G; Male; Middle Aged; Tropoelastin

Prolapsus uteri in pelvic supportive disorders are common in elderly women, and their etiology remains unclear. We examined elastin-binding proteins (EBPs) and binding sites in cultured cardinal ligament fibroblasts derived from elderly patients with prolapsus uteri (HPLiF) and compared them with those from age-matched control subjects (HCLiF). Cell attachment to alpha-elastin was significantly lower in HPLiF than in HCLiF. Elastin suppressed the higher proliferative activity at near confluency in HPLiF. The 67-kDa EBP was detectable in HCLiF, whereas HPLiF expressed a 59-kDa EBP. The expression of EBP was significantly lower in HPLiF. The synthetic peptide Val-Gly-Val-Ala-Pro-Gly (VGVAPG), which contains a recognition sequence for the elastin receptor, inhibited the adhesion of HCLiF to alpha-elastin at 10(-5)-10(-4) M, but showed no inhibitory activity on the adhesion of HPLiF at 10(-5) M. These results suggest that fibroblasts derived from elderly women with prolapsus uteri can recognize alpha-elastin through interactions with the low-molecular-size (59-kDa) EBP for the sequence VGVAPG with low affinity and may contribute to the loss of supportive function in uterine connective tissues.

Topics: Binding Sites; Cell Adhesion; Cell Division; Cells, Cultured; Collagen Type I; Collagen Type III; Connective Tissue Diseases; Elastin; Extracellular Matrix; Female; Fibroblasts; Humans; Ligaments; Pelvis; Receptors, Cell Surface

Matrix degrading enzymes are implicated in several disease processes such as abdominal aortic aneurysms and emphysema, however, monitoring proteolytic activity in a single assay is not well-established. Numerous assays have been developed to measure matrix degrading enzymes, which use artificial substrates or substrates derived from natural substrate protein. We have recently developed an assay for elastolytic activity based on the detection of primary amines, using trinitrobenzene sulfonic acid (TNBSA), following the digestion of succinylated elastin. The assay is also versatile enough to allow the detection of other proteases through the use of succinylated substrate specific for given protease. In order to improve the sensitivity and versatility of the assay we have refined the buffer conditions (PBS pH 7.2/1 mM CaCl2) to provide a 60 % increase in sensitivity to elastolytic activity and also formulated a substrate mixture containing succinylated elastin, collagen and gelatin. The combination of a substrate mixture and an optimum buffer will allow a spectrum of enzymes to be detected in a single reaction, providing a more complete picture of total proteolytic activity in a biological sample. This assay may also provide a tool to use proteolytic activity as a marker to monitor pathologic conditions involving matrix turn-over.

Topics: Buffers; Calcium Chloride; Clinical Enzyme Tests; Collagen; Connective Tissue Diseases; Elastin; Endopeptidases; Extracellular Matrix; Gelatin; Humans

Topics: Connective Tissue Diseases; Cutis Laxa; Dermis; Elastic Tissue; Elastin; Humans; Multidrug Resistance-Associated Proteins; Mutation; Pseudoxanthoma Elasticum; Williams Syndrome

Calcification of elastin occurs in many pathological cardiovascular diseases including atherosclerosis. We have previously shown that purified elastin when subdermally implanted in rats undergoes severe calcification and aluminum chloride (AlCl(3)) pretreatment of elastin inhibits calcification. In the present study we investigated whether matrix metalloproteinase (MMP) binding to elastin and elastin degradation is prevented by AlCl(3) pretreatment. Subdermal implantation of AlCl(3)-pretreated elastin showed significantly lower MMP-9 and MMP-2 activity surrounding the implant as compared to the control implants. AlCl(3) pretreatment also significantly inhibited elastin implant calcification at the seven-day implant period (AlCl(3)-pretreated 4.07 +/- 1.27, control 23.82 +/- 2.24 microg/mg; p<0.0001). Moreover, elastin gel zymography studies showed that gel pretreatment with AlCl(3) inhibited elastolysis by MMP-9. We also demonstrate significant suppression of MMP-2 activity in aortic wall segments of AlCl(3)-pretreated porcine bioprosthetic heart valve implants as compared to control valve implants in sheep mitral valve replacement studies. AlCl(3) pretreatment also significantly inhibited calcification of elastin in this model. Thus, we conclude that aluminum ion binding to elastin prevents MMP-mediated elastolysis and thus prevents elastin calcification.

Topics: Aluminum Chloride; Aluminum Compounds; Animals; Aorta; Calcinosis; Chlorides; Connective Tissue Diseases; Elastic Tissue; Elastin; Heart Valve Prosthesis; Immunohistochemistry; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Mitral Valve; Rats; Rats, Sprague-Dawley; Sheep; Swine

To delineate the molecular mechanism of transepidermal elimination of dermal elastic materials in elastosis perforans serpiginosa, the interaction between elastin and cultured keratinocytes was studied in vitro. Synthetic elastin peptide VGVAPG elicited chemotactic responses to the cultured keratinocytes at the dose of 10-9 M. Treatment of keratinocytes with 10-6 or 10-5 M elastin peptides resulted in the suppression of cell growth and the increased expression of involucrin and transglutaminase-1, markers of terminal differentiation. When cultured keratinocytes were treated with the elastin peptides, the expression of 67 kDa elastin receptor was increased. The induction of terminal differentiation by elastin peptides was attenuated by the treatment with the combination of anti-67 kDa elastin receptor antibody. The results indicate that elastin is a potent inducer of migration and terminal differentiation of cultured keratinocytes, which is mediated by the 67 kDa elastin receptor. In the lesional skins of patients with elastosis perforans serpiginosa, the 67 kDa elastin receptor was specifically expressed in the epidermis immediately surrounding the elastic materials that were being eliminated. The elastin receptor may be involved in the interaction between keratinocytes and elastin in elastosis perforans serpiginosa.

Topics: Cell Differentiation; Cell Division; Cell Movement; Chemotaxis; Connective Tissue Diseases; Elastin; Facial Dermatoses; Humans; Keratinocytes; Protein Precursors; Receptors, Cell Surface; RNA, Messenger; Transglutaminases

Topical treatment of striae rubra with 0.1% tretinoin and laser treatment of striae rubra and alba with the 585-nm pulsed dye laser are proven therapeutic options. However, little efficacy has been shown for treatment of striae alba topically, and the laser is currently not a suitable treatment option for darker ethnic skin types.. The purpose of this study was to demonstrate that selected commercial topical agents can improve the appearance of striae alba.. Ten patients of varying skin types (I-V) having straie distensae alba on the abdomen or thighs were selected to evaluate the effectiveness of two topical treatment regimens. Patients were placed on daily topical application of 20% glycolic acid (MD Forte) to the entire treatment area. In addition, the patients applied 10% L-ascorbic acid, 2% zinc sulfate, and 0.5% tyrosine to half to the treatment area and 0.05% tretinoin emollient cream (Renova) to the other half of the treatment area. The creams were applied on a daily basis for 12 weeks. Improvement was evaluated at 4 and 12 weeks in an objective unblinded fashion at the follow-up visits, a objective blinded fashion by visual grading at the conclusion of the study, and in an objective blinded fashion with profilometry. Additionally, histopathologic analysis was performed.. Analysis of these data reveals: 1) both regimens can improve the appearance of stretch marks; 2) these topical therapy regimens are safe and effective in study patients with minimal irritation; 3) elastin content within the reticular and papillary dermis can increase with topical 20% glycolic acid combined with 0.05% tretinoin emollient cream therapy; 4) both regimens increased epidermal thickness and decreased papillary dermal thickness in treated stretch marks when compared with untreated stretch marks; 5) combined epidermal and papillary dermal thickness in stretch marks treated with either topical regimen approaches that of normal skin; and 6) profilometry can objectively measure differences in skin texture associated with striae treatments when compared to controls, however, it is not sensitive enough to justify comparison or quantitative improvements between similarly effective treatments.

Topics: Abdomen; Administration, Cutaneous; Adult; Ascorbic Acid; Astringents; Atrophy; Connective Tissue Diseases; Dermatologic Agents; Drug Combinations; Elastic Tissue; Elastin; Emollients; Female; Follow-Up Studies; Glycolates; Humans; Keratolytic Agents; Middle Aged; Safety; Single-Blind Method; Skin; Thigh; Tretinoin; Tyrosine; Zinc Sulfate

We report four patients with pseudoxanthoma elasticum-like papillary dermal elastolysis (PDE). Multiple small papules on the neck, clinically resembling pseudoxanthoma elasticum, and loss of the elastic fibre network in the papillary dermis were found in each case. Immunohistochemical staining for elastin and fibrillin-1 in one patient demonstrated the disappearance of elastin and fibrillin-1 in the papillary dermis. Site-matched normal skins of the elderly showed intact elastin but a lack of fibrillin-1 in the papillary dermis. The younger normal skins revealed intact elastin and fibrillin-1. The results suggest that fibrillin-1 is absent from the papillary dermis of the normal-appearing neck skin of the elderly and that the primary defect in PDE may be in elastin rather than in fibrillin-1.

Topics: Adult; Aged; Aged, 80 and over; Connective Tissue Diseases; Elastic Tissue; Elastin; Extracellular Matrix Proteins; Female; Fibrillin-1; Fibrillins; Humans; Microfilament Proteins; Middle Aged; Pseudoxanthoma Elasticum; Skin

The purpose of this study was to determine whether elastotic degeneration of the elastin component of the lamina cribrosa occurs in optic neuropathy associated with different types of glaucoma. Human optic nerve heads with primary open-angle, neovascular, chronic angle closure and pseudoexfoliation glaucoma, and with varying duration of disease were compared with age-matched normal eyes, using electron microscopy and immunogold labeling of elastin. The percent area occupied by immunogold-labeled elastin material was determined using a digital image analysis system. In all eyes with a history of glaucoma, elastosis was found in the lamina cribrosa and there was a significantly greater percentage of area occupied by elastin compared with age-matched control eyes (P<0.0001). Among the glaucomatous eyes, pseudoexfoliation glaucoma had the largest area of elastosis, followed by primary open-angle and secondary glaucoma (neovascular and chronic angle closure). In all glaucoma samples, large, confluent elastin aggregates of irregular and varied shapes (elastosis) were observed in the lamina cribrosa and insertion region. These results demonstrate that glaucomatous optic neuropathy is associated with elastosis of the lamina cribrosa, which may contribute to the changes in compliance of the optic nerve heads of glaucomatous eyes.

Topics: Aged; Aged, 80 and over; Connective Tissue Diseases; Elastic Tissue; Elastin; Female; Glaucoma; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Optic Disk; Optic Nerve Diseases; Sclera

We describe a 15-month-old girl with Michelin tyre syndrome. She had hirsuties and marked skin folds. Histological examination showed fragmented elastic fibres in addition to smooth muscle hamartoma. On electron microscopy, decreased deposition of elastin was observed. We speculate that elastic fibre abnormalities may account for the characteristic skin changes in the Michelin tyre syndrome.

Topics: Connective Tissue Diseases; Elastic Tissue; Elastin; Female; Hirsutism; Humans; Infant, Newborn; Muscle, Smooth; Syndrome

Striae distensae are characterized by a thinning of connective tissue stroma to produce linear, atrophic-appearing skin. Excessive adrenocortical activity, genetic factors and inherited defects of connective tissues, etc. are important causative factors in the formation of striae distensae, but the basic aetiology is not known. Total RNA was extracted from skin biopsies of five patients with striae distensae. The expression of genes coding for types I and III procollagen, elastin, fibronectin and beta-actin were studied and compared with those of four sex- and age-matched healthy individuals. The percentages of types I and III procollagen mRNA were 9.9 +/- 2.9% (mean +/- s.d.) and 10.6 +/- 1.6%, respectively, of the corresponding controls. The value for fibronectin mRNA in striae distensae was 7.3 +/- 1.8% of the control. The steady-state ratio fibronectin/type I procollagen mRNAs was 0.12 +/- 0.01 in striae distensae and 0.18 +/- 0.01 in the control. These observations suggest that expression of collagens, elastin and fibronectin genes are apparently decreased, and that there is a marked alteration of fibroblast metabolism, in striae distensae.

Topics: Adolescent; Adult; Blotting, Northern; Collagen; Connective Tissue Diseases; Elastin; Female; Fibroblasts; Fibronectins; Gene Expression Regulation; Humans; Male; Procollagen; RNA, Messenger

Elastosis perforans serpiginosa (EPS) is an uncommon skin disease characterized by transepidermal elimination of abnormal elastic fibers. The disease is frequently associated with congenital connective tissue disorders or Down's syndrome. The pathogenesis of EPS is still unclear. There are a few reports in the literature about a familial occurrence of EPS in which different modes of inheritance are suggested. To support the hypothesis of a congenital origin of the disease, we have studied another family with EPS.. In this study, we describe a family in which two sisters and a brother were affected by EPS. The father and three paternal uncles were most probably affected by the same disease. There were no signs of other congenital connective tissue disease in the family members.. An autosomal dominant mode of inheritance with variable expression of EPS is suggested.

Topics: Adult; Aged; Atrophy; Cicatrix; Connective Tissue Diseases; Elastic Tissue; Elastin; Female; Humans; Keratins; Keratosis; Male; Middle Aged; Neck; Skin Diseases

Williams syndrome (WS) is a developmental disorder affecting connective tissue and the central nervous system. A common feature of WS, supravalvular aortic stenosis, is also a distinct autosomal dominant disorder caused by mutations in the elastin gene. In this study, we identified hemizygosity at the elastin locus using genetic analyses in four familial and five sporadic cases of WS. Fluorescent in situ hybridization and quantitative Southern analyses confirmed these findings, demonstrating inherited and de novo deletions of the elastin gene. These data indicate that deletions involving one elastin allele cause WS and implicate elastin hemizygosity in the pathogenesis of the disease.

Topics: Adult; Alleles; Aortic Valve Stenosis; Arteries; Blotting, Southern; Child; Child, Preschool; Chromosomes, Human, Pair 7; Connective Tissue Diseases; Developmental Disabilities; Elastin; Genes; Genotype; Humans; In Situ Hybridization, Fluorescence; Intellectual Disability; Pedigree; Sequence Deletion; Syndrome

Serum antibodies to native (tropo) and denatured (alpha) elastins appear to correlate with the production and breakdown respectively of elastic tissue. Elastin may be degraded as a part of autoimmune diseases. This possibility was tested by measuring IgG antibodies to tropo- and alpha-elastins by ELISA in the sera of 111 patients with a variety of connective tissue diseases compared with 18 healthy individuals. Anti-alpha-elastin antibodies were significantly higher in sera from 18 scleroderma patients than from healthy controls (p less than 0.008). Conversely, anti-tropoelastin antibody levels for scleroderma patients (p less than 0.03) and for patients with a variety of other connective tissue diseases (p less than 0.02) were lower than in healthy controls. Low antibody levels to native elastin and high levels of antibodies to denatured elastin suggest a low synthesis: degradation ratio for elastin in scleroderma. Scleroderma may be a unique model for elastin turnover because of its heretofore unrecognized accelerated elastolysis.

Topics: Adolescent; Adult; Antibodies; Connective Tissue Diseases; Elastin; Humans; Immunoglobulin G; Middle Aged; Scleroderma, Systemic; Tropoelastin

Buschke-Ollendorff syndrome (BOS; McKusick 16670) is an autosomal dominant connective-tissue disorder characterized by uneven osseous formation in bone (osteopoikilosis) and fibrous skin papules (dermatofibrosis lenticularis disseminata). We describe two patients in whom BOS occurred in an autosomal dominant inheritance pattern. The connective tissue of the skin lesions showed both collagen and elastin abnormalities by electron microscopy. Cultured fibroblasts from both patients produced 2-8 times more tropoelastin than normal skin fibroblasts in the presence of 10% calf serum. Involved skin fibroblasts of one patient produced up to eight times normal levels, whereas apparently uninvolved skin was also elevated more than threefold. In a second patient, whose involvement was nearly complete, elastin production was high in involved areas and less so in completely involved skin. Transforming growth factor-beta 1 (TGF beta 1), a powerful stimulus for elastin production, brought about similar relative increases in normal and BOS strains. Basic fibroblast growth factor, an antagonist of TGF beta 1-stimulated elastin production, was able to reduce elastin production in basal and TGF beta 1 stimulated BOS strains. Elastin mRNA levels were elevated in all patient strains, suggesting that Buschke-Ollendorff syndrome may result, at least in part, from abnormal regulation of extracellular matrix metabolism that leads to increased steady-state levels of elastin mRNA and elastin accumulation in the dermis.

Topics: Blotting, Southern; Cells, Cultured; Connective Tissue Diseases; Elastin; Female; Fibroblast Growth Factor 2; Fibroblasts; Humans; Male; Microscopy, Electron; Middle Aged; Nevus; Osteopoikilosis; Pedigree; Phenotype; RNA, Messenger; Skin; Skin Neoplasms; Syndrome; Transforming Growth Factor beta

The spontaneous rupture of the internal elastic lamina (IEL) in various arteries occurs to different extents in different rat strains. We have quantified this phenomenon in the caudal and renal arteries and abdominal aorta in two normotensive inbred strains: the Brown Norway (BN) and Long Evans (LE) strains. At 5 weeks of age, BN rats of both sexes exhibited small numbers of interruptions in the IEL of the caudal artery, whereas LE rats did not. Postpubertal male and female BN rats presented large numbers of IEL interruptions in the caudal artery and significant numbers in the renal artery and abdominal aorta, whereas LE rats showed few in the caudal artery and none in the other arteries. Treatment with beta-aminopropionitrile (BAPN, an inhibitor of lysyl oxidase, the enzyme involved in the formation of cross-links in elastin and collagen) increased the formation of IEL ruptures in both strains in the caudal and renal artery and in the abdominal aorta in BN rats, but not in the abdominal aorta of LE rats. Apart from IEL ruptures, which were more prevalent in BN rats, no differences were observed in the ultrastructure of the aortic elastic fibers between the two strains, either in controls or in BAPN-treated rats. When male rats of both strains were made hypertensive by unilateral nephrectomy and administration of deoxycorticosterone and salt, mortality was more precocious in the BN strain although blood pressure was significantly higher in the BN strain at only one time point. The incidence of cerebrovascular hemorrhage was 48% in BN rats and 0% in LE rats. Hypertension increased the formation of ruptures in the IEL in some arteries - to a greater extent in the BN than in the LE rats. These results raise the possibility that the propensity to spontaneous rupture of the IEL, which is in part genetically determined, may reflect a latent form of vascular fragility which becomes significant in hypertension, resulting in poor survival and susceptibility to cerebrovascular accidents.

Topics: Aminopropionitrile; Aneurysm; Animals; Connective Tissue Diseases; Elastic Tissue; Elastin; Female; Hypertension; Longevity; Male; Protein-Lysine 6-Oxidase; Rats; Rats, Inbred BN; Rupture, Spontaneous; Species Specificity; Vascular Diseases

Elastosis in benign and malignant breast lesions was studied by light microscopic immunohistochemistry for elastin and by electron microscopy. Upon immunohistochemical examination for elastin, elastosis, particularly in scirrhous-type ductal carcinoma, showed two characteristic staining patterns: fibrously and intensely stained elastic fibers and evenly stained elastic masses. Elastic fibers showing increased fibrous staining occurred mainly in the stromal areas, and were considered to be newly formed because they consisted of tannic acid-positive amorphous components and abundant microfibrils. Evenly stained elastic masses were observed mainly in the periductal areas and showed less intense stainability. These masses consisted of numerous fine amorphous components with plentiful microfibrils. In some regions within these masses, there were condensed accumulations of irregularly arranged small amorphous components associated with only a few microfibrils. These amorphous components had an ill-defined outline and were occasionally associated with spiralling collagen fibrils and cell debris. On the basis of these findings, the periductal evenly stained elastic masses were thought to be formed by excessive production of elastic fibers and degradation of pre-existing and newly formed elastic fibers.

Topics: Breast Neoplasms; Carcinoma; Connective Tissue Diseases; Elastic Tissue; Elastin; Humans; Immunohistochemistry; Microscopy, Electron; Reference Values; Skin Diseases

Topics: Collagen; Connective Tissue; Connective Tissue Diseases; Elastin; Humans; Proteoglycans; Skin Diseases

In two cases of elastosis perforans serpiginosa (EPS) new clinical and laboratory data are described and discussed. In Case 1, EPS was triggered by penicillamine-D within an unusually short period (about one year). In Case 2, EPS was apparently primarily triggered by a vena puncture. In both cases the light and electron microscopic findings were strictly compatible with EPS. These findings are summarized. In the active lesions of both cases increased numbers of helper T-cells and Langerhans cells were shown, while cytotoxic-suppressor T-cells were nearly completely absent. Leu 3a+ cells and Leu 6+ cells were also present in the inactive central area of the lesions. The data presented may cast doubt on the relationship of immunological findings to pathogenetic events in the disease.

Topics: Adult; Connective Tissue Diseases; Elastin; Female; Humans; Male; Skin Diseases

Topics: Collagen; Connective Tissue Diseases; Elastic Tissue; Elastin; Fragile X Syndrome; Humans; Intellectual Disability; Male; Sex Chromosome Aberrations; Skin

Pectus excavatum is a common malformation in diseases of elastic tissue (Marfan, Ehlers-Danlos...). When observed apparently alone it may represent a minor form of dystrophy, implying the same risk of a cardiac lesion. Abnormalities of the thoracic skeleton and echocardiographic mitral valve prolapse is a well established association, suggesting a common disorder of connective tissue. However, there is no absolute proof that this is a statistically significant association. Histological connective tissue changes relating these two markers have yet to be found. Clinical and echocardiographic examinations and skin biopsies were performed in 17 patients with pectus excavatum. Mitral valve prolapse was detected in 65% of cases (associated in 1 out of 3 cases with tricuspid valve prolapse). In 53% of cases electron microscopy showed abnormal skin collagen and elastin. Collagen abnormalities were twice as common as those of elastin and could be associated. Mixed changes of thinning of elastin and collagen fibres of irregular calibre were particularly suggestive. Pectus excavatum would therefore seem to be the expression of a minor form of dystrophy of collagen and elastin tissues and a clinical marker of possible mitral valve prolapse.

Topics: Adult; Collagen; Connective Tissue; Connective Tissue Diseases; Echocardiography; Elastin; Female; Funnel Chest; Humans; Male; Microscopy, Electron; Mitral Valve Prolapse

Topics: Collagen; Collagen Diseases; Connective Tissue Diseases; Elastic Tissue; Elastin; Humans; Keloid; Microbial Collagenase; Neoplasm Invasiveness; Proteoglycans; Wound Healing

Topics: Animals; Collagen; Connective Tissue; Connective Tissue Diseases; Elastin; Humans; Lung; Pulmonary Emphysema; Pulmonary Fibrosis; Smoking

The development of immunity to homologous connective tissue antigens was studied with respect to aging in the tight-skin (Tsk) mouse mutant. A delayed-type hypersensitivity (DTH) response to elastase-solubilized lung peptides in Tsk/+ mice, which became evident at 10 weeks of age and increased in intensity until 22 weeks, was observed. Tsk mice did not demonstrate significant DTH responses when challenged with type I or IV collagen, and normal (+/+) littermates of all ages did not respond to any of the antigens under study. DTH responses could be adoptively transferred to normal +/+ and C57BL/6 mice with spleen cells from 30-week-old Tsk/+ mice; treatment with anti-Thy 1.2 antibodies plus complement significantly reduced the ability of these Tsk/+ cells to transfer DTH reactivity. No antibody activity to the antigens under study could be detected in the sera of Tsk/+ or +/+ mice at any age. These results are discussed with regard to the pathological manifestations observed in the Tsk/+ mutant mouse.

Topics: Aging; Animals; Collagen; Connective Tissue Diseases; Elastin; Hypersensitivity, Delayed; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; T-Lymphocytes

Normal, human dermis is a dense, interwoven collagen and elastic matrix organized into papillary and reticular regions. the papillary dermis is a narrow zone beneath the epidermis which includes an even narrower subepidermal connective tissue band beneath the basal lamina. The reticular dermis has superficial intermediate and deep reticular zones. Each region is distinguished by the organization of the fibrous connective tissue. In this review, the structure, composition and function of each region of the normal dermis is surveyed and alterations in the tissue that have been recognized ultrastructurally in skin from patients with inherited connective tissue diseases are discussed. A molecular defect in a connective tissue molecule can be expressed phenotypically at one or more levels of dermal organization and can modify the structure of other matrix components. In some cases, the entire interwoven pattern of the dermis is altered; in others, the dermis retains the interwoven pattern and alterations are expressed as defects in the association of fibrils into fibers and fiber bundles. Abnormalities in the size, packing and relationships of fiber bundles also can occur. These changes involve the collagen matrix primarily. Depletion or exaggeration of elastin, or of the amorphous ground substance can also influence the organization of collagen and of the overall dermal architecture. The alterations described are illustrated with scanning electron micrographs of skin from patients with inherited connective disorders and are discussed in terms of the mechanical abnormalities of the tissue.

Topics: Collagen; Connective Tissue; Connective Tissue Diseases; Cytoskeleton; Elastin; Glycoproteins; Glycosaminoglycans; Humans; Microscopy, Electron, Scanning; Skin

Previous morphologic observations have suggested abnormalities in the elastic fibers in a number of both inherited and acquired diseases. Recent progress made in understanding of the normal biology of elastin has allowed us to examine these diseases by biochemical means. In this review we are discussing the current status of the research on the elastin diseases with particular emphasis on clinical conditions affecting skin, as for example, cutis laxa, pseudoxanthoma elasticum, and the Buschke-Ollendorff syndrome. In addition, we present new data which appears to be the first demonstration of an elastin abnormality in the Marfan syndrome.

Topics: Connective Tissue Diseases; Cutis Laxa; Elastin; Humans; Marfan Syndrome; Menkes Kinky Hair Syndrome; Pseudoxanthoma Elasticum; Skin; Skin Diseases

Both iron and copper play critical biochemical roles in the post-translational modifications of collagen and elastin. These modifications are essential to the maturation and structural integrity of these proteins. Iron functions in the hydroxylation of specific prolyl and lysyl residues in collagen, a process that must occur before the triple helix can form and be extruded from the cell. Copper functions in the oxidative deamination of specific lysyl residues in the soluble forms of both elastin and collagen. This process is essential for crosslink formation and the structural integrity of these proteins. While there is no evidence that nutritional iron deficiency results in connective tissue pathology, copper deficiency impairs crosslink formation and results in gross pathology of bones, lungs and the cardiovascular system of many animal species.

Topics: Animals; Ascorbic Acid; Collagen; Connective Tissue; Connective Tissue Diseases; Copper; Elastin; Humans; Hydroxylation; Iron; Protein Precursors; Protein-Lysine 6-Oxidase

Topics: Animals; Aorta; Body Water; Collagen; Connective Tissue; Connective Tissue Diseases; DNA; Elastin; Glycosaminoglycans; Lipid Metabolism; Male; Prednisolone; Proteins; Rabbits; RNA; Skin

The connective tissue, composed of cells, fibers and ground substance, plays a vital role in the processes of craniofacial development, growth, wound healing and disease. This article reviews current knowledge of connective tissue biology and relates it to certain clinical situations of relevance in oral surgery.

Topics: Amino Acids; Animals; Collagen; Connective Tissue; Connective Tissue Diseases; Elastin; Humans; Maxillofacial Development; Rabbits; Rats; Tooth; Wound Healing

Topics: Connective Tissue Diseases; Ehlers-Danlos Syndrome; Elastic Tissue; Elastin; Humans; Pseudoxanthoma Elasticum