elastin and Diabetes-Mellitus

The extracellular matrix (ECM) provides a scaffold for cells, controlling biological processes and providing structural as well as mechanical support to surrounding cells. Disruption of ECM homeostasis results in several pathological conditions. Skeletal muscle ECM is a complex network comprising collagens, proteoglycans, glycoproteins, and elastin. Recent therapeutic approaches targeting ECM remodeling have been extensively deliberated. Various ECM components are typically found to be augmented in the skeletal muscle of obese and/or diabetic humans. Skeletal muscle ECM remodeling is thought to be a feature of the pathogenic milieu allied with metabolic dysregulation, obesity, and eventual diabetes. This narrative review explores the current understanding of key components of skeletal muscle ECM and their specific roles in the regulation of metabolic diseases. Additionally, we discuss muscle-specific integrins and their role in the regulation of insulin sensitivity. A better understanding of the importance of skeletal muscle ECM remodeling, integrin signaling, and other factors that regulate insulin activity may help in the development of novel therapeutics for managing diabetes and other metabolic disorders.

Topics: Animals; Collagen; Diabetes Mellitus; Elastin; Extracellular Matrix; Homeostasis; Humans; Insulin Resistance; Integrins; Laminin; Metabolic Diseases; Mice; Muscle, Skeletal; Rats

Arterial stiffening is a progressive, ubiquitous and irreversible aging process that is interwoven with and accelerated by various diseases such as diabetes, atherosclerosis and hypertension. In large arteries, aging is characterized by decreased turnover of collagen and elastin and increased advanced glycation end-products (AGEs) and cross-links. Elastic fibers undergo lysis and disorganization subsequent to their replacement by collagen and other matrix components. These events cause the loss of elasticity and induce stiffening. Conceptual approaches to minimize AGE accumulation in arteries include caloric restriction, exercise, low dietary intake of AGEs, deglycation enzymes, increased clearance of AGEs, antagonists of AGE receptors and pharmaceutical interventions. Much optimism exists in the ability of 'AGE breakers' such as alagebrium (ALT-711) to cleave AGE cross-links and reverse the age-related stiffening of arteries. However, there is little evidence that these agents actually break pre-existing AGE cross-links in vivo. In contrast, many of these anti-AGE agents share in common the ability to chelate metals, thus acting as inhibitors of metal-catalyzed AGE and protein carbonyl formation. Future work on interventions into the causes of arterial stiffness in aging needs to address more rigorously the relationship between stochastic forms of damage, such a glycation and oxidation, and the changes in elastic fiber structure thought to contribute to loss of arterial elasticity.

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Collagen; Diabetes Mellitus; Disease Progression; Elastin; Female; Geriatric Assessment; Glycation End Products, Advanced; Glycosylation; Humans; Hypertension; Male; Molecular Biology; Prognosis; Risk Assessment; Vascular Stiffness

The microangiopathy under hyperglycemia and diabetes develops only in the microcirculation component of circulatory system. In this area considerable amount of pericytes is concentrated. These cells contain myofibrils and in circulatory mode envelop capillaries being situated on the outside of basilemma. It is possible that in a phylogenetic sense this is the earliest functional unity of endothelium monolayer as a pacemaker and pericytes as contractile elements which are the earliest "propeller" because of implementing the function of advancement of lymph, hemolymph and blood in capillaries. Probably, endothelium and pericytes formed the first variation of peristaltic "pump" for the purpose of blood advancement longwise of capillaries. Most probably, the state of distal part of arterial race (muscular type arterioles) impact the parameters of proximal part of arterial race (elastic type arterioles) and myocardium itself in the same extent as the state of "pump" in capillaries, endothelium and pericytes function impact the function of local peristaltic pumps (muscular type arterioles) in paracrine cenosis. It is supposed that the pericytes are the regulators of physical, hydraulic factor of activation of biologic reaction of transcitosis--excretion of nutrients and humoral mediators from capillaries to the pool of intercellular medium to perform the biologic function of homeostasis. Hyperglycemia, glycotoxins formation, bivalent substances (glyoxal, methilglyoxal, malonic dialdehyde) reacting simultaneously by both ends of molecule result in formation within collagen of areolar tissue of short transversal cross-links (glycosylation end product) which significantly increase rigidity (hardness) of capillary wall. In these conditions, myofibrils of pericytes no longer form directed deformation of capillary wall to effect peristalsis and advancement of hemolymph (blood later on) along capillaries according the synthesis of monolayer endothelium NO as a dilatation factor. This is the cause of blood circulation disturbance on the level of exchange capillaries and formation of chronic hypoxemia resulting in the only increase of rate of glycosylation chemical reaction. The microangiopathy is formed in the cells and tissues in an integrated pool of intercellular medium and never occurs in the cerebrospinal fluid pool where no hyperglycemia develops.

Topics: Arterioles; Capillaries; Cell Communication; Collagen; Diabetes Mellitus; Diabetic Angiopathies; Elastin; Extracellular Matrix; Glycation End Products, Advanced; Glycosylation; Humans; Hyperglycemia; Hypoxia; Pericytes

Glycemia is a physiological parameter tightly regulated for an optimal energetic supply to the organism, in spite of variable tissular glucose needs. Physiopathological alteration of glycemic regulation leads to dysfunctions of many cell types. For example, diabetes considerably increases morbidity and mortality linked to cardiovascular pathologies and constitute nowadays a serious public health problem. Many in vivo and in vitro studies have investigated the impact of extracellular glucose concentration on smooth muscle and endothelial cells. Glycemia regulates expression and activity of proteins implicated in various processes, such as vasodilation (eNOS), cellular adherence (ICAM-1, VCAM-1), glucose transport (GLUT-1) or free radical generation. Nuclear receptors of the PPAR (peroxisome proliferator-activated receptors) family which are implicated in glucose and lipid metabolism control, seem to have direct vascular actions, in the regulation of cellular functions by extracellular glucose, reinforcing their status of pharmacological targets for preservation and improvement of vascular function. More general processes, such as cellular proliferation and cell death, are also influenced by glucose concentration. Concerning the contractile function, hypoglycemia and hyperglycemia modulate vascular reactivity while acting on the vasoactive substances level and the cellular response to these molecules. In particular they act on variation of ionic channels (K+, Ca2+) activity or by interfering with some signaling pathways (NO). For example, the age-dependant vasodilation and endothelial calcium influx induced by elastin peptide are modulated by extracellular glucose levels. In conclusion, abnormal chronic variations of circulating glucose levels seem to be directly responsible for endothelial and smooth muscle cell dysfunction in the pathogenesis of cardiovascular abnormalities of patients presenting glycemia dysregulations.

Topics: Aging; Animals; Apoptosis; Blood Glucose; Blood Vessels; Calcium Signaling; Cell Adhesion; Cell Division; Diabetes Mellitus; Elastin; Endothelium, Vascular; Gene Expression Regulation; Glucose; Humans; Hyperglycemia; Ion Channels; Muscle, Smooth, Vascular; Peroxisome Proliferators; Signal Transduction; Vasodilation

The most serious late complication of ageing and diabetes mellitus follow similar patterns in the dysfunction of retinal capillaries, renal tissue, and the cardiovascular system. The changes are accelerated in diabetic patients owing to hyerglycaemia and are the major cause of premature morbidity and mortality. These tissues and their optimal functioning are dependent on the integrity of their supporting framework of collagen. It is the modification of the properties by glycation that results in many of the damaging late complications. Initially glycation affects the interactions of collagen with cells and other matrix components, but the most damaging effects are caused by the formation of glucose-mediated intermolecular cross-links. These cross-links decrease the critical flexibility and permeability of the tissues and reduce turnover. In contrast to the renal and retinal tissue, the cardiovascular system also contains a significant proportion of other fibrous connective tissue protein elastin, and its properties are similarly modified by glycation. The nature of these glycation cross-links is now being unravelled and this knowledge is crucial in any attempt to inhibit these deleterious glycation reactions.

Topics: Aging; Animals; Arginine; Collagen; Cross-Linking Reagents; Diabetes Complications; Diabetes Mellitus; Elastin; Glycation End Products, Advanced; Glycosylation; Humans; Imidazoles; Lysine; Maillard Reaction; Malondialdehyde; Norleucine; Pyrroles

Recent concepts on the mechanisms of aging of extracellular matrix (EM) are reviewed as well as its involvement in age-associated diseases. Cell differentiation, histogenesis and organogenesis can be analyzed in terms of the program of the biosynthesis of EM macromolecules during development, maturation and aging. The most important biological role of EM is the integration of cells in tissues, of tissues in organs and of organs in the whole organism. EM can directly influence cell behavior through the contact between EM and the genome mediated by structural glycoproteins (fibronectin, laminin, elastonectin, etc.) interacting with other EM macromolecules (collagen, proteoglycans, elastin) and the cytoskeleton by trans-membrane receptors (integrins). Most age-associated diseases exhibit a deviation (qualitative or quantitative) from the normal program of EM biosynthesis. Three examples are analyzed in some detail: atherosclerosis, diabetes and malignant tumors. The degradation of elastic fibers catalyzed by cellular elastase-type enzymes is observed in atherosclerosis and also in emphysema and skin aging. Several of these enzymes were isolated and characterized from platelets, fibroblasts, smooth muscle cells and lipoproteins. The biosynthesis of some of them increases with age and facilitates cell migration. Plasma fibronectin increases with age exponentially. This increase is absent or strongly attenuated in diabetes and some cancers. Tissue fibronectin increases in diabetes, Werner syndrome and in the peritumoral desmoplastic reaction while most tumor cells can no more retain fibronectin on their membrane facilitating their movement in the organism. These examples demonstrate the importance of the study of cell matrix interactions for gerontology.

Topics: Aging; Arteriosclerosis; Cell Differentiation; Diabetes Mellitus; Elastin; Extracellular Matrix; Fibronectins; Humans; Neoplasms

Diabetes mellitus induces alterations in the metabolism of the macromolecules present in the intercellular matrices and particularly in the basement membranes. These contribute to the morphological changes characteristic of the disease : basement membrane thickening, skin thickening and induration. Accumulation of overglycosylated collagens and diminution of sulfated proteoglycan concentrations are the most generally reported biochemical modifications in human or animal diabetic states. More limited data are available concerning elastin, fibronectin and laminin in diabetes.

Topics: Animals; Basement Membrane; Collagen; Connective Tissue; Diabetes Mellitus; Elastin; Extracellular Matrix; Glycoproteins; Glycosaminoglycans; Humans; Proteoglycans; Skin; Tissue Distribution

In studies concerning risk factors for cardiovascular diseases, a number of reports have emphasized the influence of lipids, but the role of dietary minerals other than sodium has been less studied. However, epidemiological studies have suggested that dietary intake of magnesium and potassium may be involved in such pathogenesis. Studies of the influence of magnesium deficiency on arteriosclerosis include its effect on the initial lesion, altered metabolism of elastin, proliferation of collagen, calcification, lipid metabolism, platelet aggregation and hypertension. Magnesium and potassium metabolism are closely related and magnesium is required for maintaining the level of cellular potassium. As a consequence, magnesium and potassium deficiency frequently occur together and potassium deficiency may be an aggravating factor in pathogenesis. The development of the initial lesion in the arterial wall may be facilitated by loss of cellular magnesium and potassium. Experimental magnesium deficiency induces arterial damage, a loss of magnesium and potassium and an increase in the calcium and sodium content of the cell. Experimental models that have been used to produce cardiovascular lesions induce similar changes and losses of major intracellular cations may affect the main metabolic processes of the cell. This report summarizes the experimental evidence that magnesium deficiency may affect several different stages involved in arteriosclerosis and that potassium deficiency may exacerbate this. Magnesium deficiency results in vascular calcification. Experiments indicate that elastin is the site of the initial calcification and the metabolism of elastin is altered. This vascular lesion then brings about an increase in the collagen content of the wall. Low magnesium status could probably affect this process by slowing collagen resorption and lead to an irreversible accumulation of connective tissue. Results showing a different distribution of the various types of lipoprotein during experimental magnesium deficiency strongly suggest that lipid exchange between the vessel walls and blood can be modified. Severe magnesium deficiency in weanling rats produces a marked hypertriglyceridemia, a decrease in the percentage of cholesterol transported by HDL lipoprotein and a reduction in LCAT activity. The decreased clearance of circulatory triglycerides appears to be the major mechanism contributing to hyperlipemia. Magnesium deficiency could therefore contribute to accu

Topics: Animals; Arteriosclerosis; Blood Platelets; Calcinosis; Collagen; Diabetes Mellitus; Diet; Elastin; Humans; Hypertension; Lipid Metabolism; Lipoproteins; Magnesium; Magnesium Deficiency; Muscle, Smooth, Vascular; Potassium; Potassium Deficiency; Rats; Thrombosis

Diabetes affects the microcirculation, the large arteries and occasionally the large and small veins, by inducing vessel wall sclerosis. The degree of stiffening produced is linked to its duration. The ability of the diabetic's circulation to distribute blood is affected, especially during increased blood flow. In most tissues this causes no serious burden, but three tissues are unusually susceptible to disturbance--the retina, renal cortex, and peripheral nerve. They develop serious problems in many longstanding diabetics. Damage to the kidney appears to be linked to its unique combination of high blood flow rate and precise control of intraglomerular filtration pressure. As renal arteriolar intima hyalinizes, the glomerular mesangium increases in volume. Diabetic renal changes appear to become irreversible when a critical stage, manifested be albuminuria and hypertension, is reached. The resulting renal failure is associated with clumpy deposits of type IV collagen in the cortex, suggesting that local microvascular autoregulation has been lost. The retinal circulation forms late in fetal life in a process in which local oxygen tension controls new vessel formation. In adult diabetics, local retinal oxygenation is disrupted by a condition called capillary closure, and intraretinal microaneurysms form. In advanced retinopathy, new microvessel systems grow into the vitreous through defects in the internal limiting membrane, producing hemorrhage and vitreous opacification. Macular degeneration is also seen in older diabetics, suggesting that the choroidal circulation may also be compromised. Evidence for a microcirculatory role in diabetic peripheral nerve damage is not as conclusive as for the kidney and retina. The longest peripheral nerves are typically the most affected. Recent studies suggest that nerve damage can be produced by a disturbance in local pressure-flow relationships combined with epineurial mechanical constraint. Hypotheses about the pathogenesis of diabetic vascular sclerosis are reviewed, including collagen-stiffening, elastin degeneration, hemorheologic burden, metabolic disruption, increased permeability, and auto-immune disturbance.

Topics: Capillary Permeability; Chronic Disease; Collagen; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Elastin; Glomerular Filtration Rate; Humans; Microcirculation; Regional Blood Flow; Renal Circulation; Retinal Vessels; Time Factors

Topics: Aging; Animals; Blood Proteins; Carbohydrate Metabolism; Collagen; Crystallins; Diabetes Mellitus; Elastin; Glucose; Glycated Hemoglobin; Glycolysis; Hot Temperature; Humans; Lysine; Models, Biological; Proteins

Annular elastolytic giant cell granuloma (AEGCG) is a rare granulomatous skin condition. It belongs to a group of skin and elastic fiber disorders. When it affects sun-exposed skin, it is also called actinic granuloma. The etiology and pathogenesis are still debated. However, sun-induced actinic damage to elastic fibers is acknowledged as the primary triggering factor, though the pathogenesis of instances in sun-covered areas is unknown. The most commonly linked systemic illness is diabetes mellitus. Different case reports show an association of this disease with hematological conditions, infections, sarcoidosis, and protoporphyria. Multisystemic involvement was also reported in a case. The disease is clinically recognized by erythematous non-scaly annular patches and plaques with raised borders and hypopigmented or skin-colored centers, sometimes atrophic. It is usually asymptomatic or mildly itchy. The presence of an inflammatory infiltration with non-palisading granulomas, multinucleate large cells, elastin degradation, and elastophagocytosis, as well as the absence of necrobiosis and mucin, are histopathological characteristics. We report a 5-year history of annular elastolytic giant cell granuloma in a 66-year-old woman with a history of type two diabetes mellitus, hypertension, and fatty liver disease (steatosis). She presented with asymptomatic polymorphic erythematous skin lesions mainly in sun-exposed areas.

Topics: Aged; Diabetes Mellitus; Elastin; Female; Granuloma, Giant Cell; Humans; Metabolic Syndrome; Mucins; Photosensitivity Disorders

Ascending aorta aneurysms (AsAA) are associated with a degeneration of the aortic wall tissue, which leads to changes in tissue mechanical properties. Risk factors for the development of the AsAA disease are recognized in patient age and gender, valve type, hypertension, diabetes mellitus, smoking history, and a prior diagnosis of Marfan syndrome. The present study aims to assess how such clinico-pathological factors can affect the mechanical properties of human dilated ascending aorta. Specimens of AsAA are excised from 68 patients who underwent elective AsAA surgical repair and stretched until rupture during the execution of uniaxial tensile tests. Experimental stress-stretch curves are used to determine tissue mechanical properties (stress and stretch at failure point and at transition point, low and high elastic modulus). Data are divided into groups according to region (anterior vs posterior), direction (circumferential vs longitudinal), and then according to age (young vs old), gender (male vs female), valve type (tricuspid aortic valve, TAV, vs bicuspid aortic valve, BAV), and presence of hypertension, diabetes mellitus, and/or Marfan syndrome (yes/no). Moreover, data are grouped according to the critical value of body mass index (BMI), maximum AsAA diameter, and aortic stiffness index (ASI), respectively. Finally, a non-parametric statistical analysis is performed to find possible significant differences and correlations between mechanical properties and clinico-pathological data. Our results confirm the anisotropy and heterogeneity of the AsAA tissue and highlight that ageing and hypertension make the AsAA tissue weaker and less extensible, whereas the valve type affects the tissue strength with higher values in BAV than in TAV patients. No effects of gender, critical BMI, critical maximum AsAA diameter, critical ASI, smoking status, and presence of diabetes mellitus, and Marfan syndrome are evidenced.

Topics: Aged; Anisotropy; Aorta; Aortic Aneurysm, Thoracic; Aortic Valve; Bicuspid Aortic Valve Disease; Biomechanical Phenomena; Body Mass Index; Body Weight; Collagen; Diabetes Mellitus; Elastin; Female; Heart Valve Diseases; Humans; Hypertension; Male; Marfan Syndrome; Middle Aged; Models, Statistical; Risk Factors; Stress, Mechanical; Tensile Strength; Vascular Stiffness

Chronic skin wounds are characterized by poor re-epithelialization, angiogenesis and granulation. Previous work has demonstrated that topical stromal cell-derived growth factor-1 (SDF1) promotes neovascularization, resulting in faster re-epithelialization of skin wounds in diabetic mice. However, the clinical usefulness of such bioactive peptides is limited because they are rapidly degraded in the wound environment due to high levels of proteases. Here, we describe the development of a recombinant fusion protein comprised of SDF1 and an elastin-like peptide that confers the ability to self-assemble into nanoparticles. The fusion protein and recombinant human SDF1 showed similar binding characteristics, as indicated by the measured equilibrium dissociation constant (Kd) for the binding of free SDF1 or the fusion protein to the CXCR4 receptor. The biological activity of SDF1-ELP, as measured by intracellular calcium release in HL60 cells was dose dependent, and also very similar to that of free SDF1. In contrast, the biological activity of SDF1-ELP in vivo was significantly superior to that of free SDF1. When applied to full thickness skin wounds in diabetic mice, wounds treated with SDF1-ELP nanoparticles were 95% closed by day 21, and fully closed by day 28, while wounds treated with free SDF1, ELP alone, or vehicle were only 80% closed by day 21, and took 42days to fully close. In addition, the SDF1-ELP nanoparticles significantly increased the epidermal and dermal layer of the healed wound, as compared to the other groups. These results indicate that SDF1-ELP fusion protein nanoparticles are promising agents for the treatment of chronic skin wounds.

Topics: Animals; Chemokine CXCL12; Diabetes Mellitus; Elastin; HL-60 Cells; Humans; Mice, Transgenic; Nanoparticles; Peptides; Receptors, CXCR4; Recombinant Fusion Proteins; Skin; Wound Healing

The present investigations arose from our interest in the possibility that some structures which arise secondary to protein glycation might bind transition metals such as iron and copper. In support of this we find that, when glycated, three different proteins--albumin, gelatin (a soluble collagen fragment) and elastin--all gain a substantial affinity for the transition metals iron and copper. The glycated proteins bind at least three times as much iron as do the non-glycated proteins. Similarly, glycated albumin and gelatin also bind 2-3 times as much copper. Furthermore, at least in the case of copper bound to glycated albumin, the bound metal retains redox activity and participates in the catalytic oxidation of ascorbic acid. Should similar "glycochelates" form in vivo in diabetics, reactions mediated by these chelates may be involved in certain complications of diabetes.

Topics: Albumins; Ascorbic Acid; Chelating Agents; Copper; Diabetes Complications; Diabetes Mellitus; Elastin; Gelatin; Humans; Iron; Oxidation-Reduction; Protein Binding

The differences in desmosine, isodesmosine (DID), hydroxyproline and cholesterol in the human thoracic aorta from diabetic (n = 16) and non-diabetic (n = 17) autopsy subjects were investigated. DID was analyzed by the use of high performance liquid chromatography. The amount of DID, and total DID (DID+reduced DID) tended to be lower in the diabetic than in non-diabetic subjects. The ratio of DID or total DID to hydroxyproline was significantly decreased in diabetic compared to non-diabetic subjects. Amount of DID, reduced DID and total DID were significantly lower in aorta with plaque formation than that without plaque or ulcer. Multiple regression analysis showed that amount of cholesterol, DID, reduced DID and age were significantly associated with dry weight per area of the aorta. A similar association was not observed in non-diabetic subjects. Compositional changes of aortic cholesterol and elastin have a closer relationship with atherosclerosis in diabetic than in non-diabetic subjects.

Topics: Adult; Aged; Aged, 80 and over; Aorta, Thoracic; Cholesterol; Chromatography, High Pressure Liquid; Desmosine; Diabetes Mellitus; Elastin; Female; Humans; Hydroxyproline; Isodesmosine; Male; Middle Aged

The degradation of elastin during various pathological processes such as emphysema or arteriosclerosis was demonstrated by several investigators. In the present work, we adapted an ELISA technique for the determination of elastin peptide (EP) levels in human sera and plasma, in healthy and arteriosclerotic subjects. This test makes use of human aorta elastin hydrolyzed by a chemical procedure (kappa-elastin) instead of EP produced by pancreatic or leukocyte elastase. Polyclonal antibodies to this antigen were obtained in rabbits. The indirect ELISA procedure is sensitive, specific and reproducible. No correlation could be demonstrated between EP level and anti-EP antibody concentration of IgG or IgM types determined in the same serum samples. These antibodies did not interfere with EP determinations. EP concentration did not change with age in control subjects. In obliterative arteriosclerosis of the legs and in type IIb hyperlipoproteinemia, EP levels showed a marked increase, while in hypertension, ischemic heart disease and diabetes mellitus, the increase was moderate. In stroke, only slight changes were observed. In type IV hyperlipoproteinemia, EP levels were lower than in controls.

Topics: Adult; Age Factors; Aged; Aorta; Arteriosclerosis; Cerebrovascular Disorders; Coronary Disease; Diabetes Mellitus; Elastin; Enzyme-Linked Immunosorbent Assay; Humans; Hydrolysis; Hyperlipoproteinemias; Hypertension; Immunoglobulin G; Immunoglobulin M; Leg; Middle Aged; Peptides; Sensitivity and Specificity

We adapted a highly sensitive and reproducible ELISA technique for the determination of anti-elastin peptide antibodies of IgG type AEAb-IgG) and IgM type AEAb-IgM) in human sera. The determination was performed in the sera of 265 normal and diseased persons. The pathologies studied included obliterative arteriosclerosis of the legs, ischemic heart disease, stroke, diabetes mellitus, type IIb and IV hyperlipoproteinemia and hypertension. No clearcut correlation could be found between AEAb and age. In contrast, in arteriosclerotic patients and especially in obliterative arteriosclerosis of the legs and ischemic heart disease, the concentration of AEAb-IgG was significantly increased. The AEAb-IgM showed no change in the studied diseases. Both types of AEAb were decreased in type IV hyperlipoproteinemia. Anti-elastin antibodies may be involved in the pathomechanisms of the above diseases and the determination of antibody concentrations may be of some help in obliterative arteriosclerotic diseases.

Topics: Adult; Aged; Antibodies; Arteriosclerosis; Cerebrovascular Disorders; Coronary Disease; Diabetes Mellitus; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type IV; Male; Middle Aged; Peptides

In order to further investigate the role of the immune system in the arteriosclerotic process, we investigated the anti-elastin peptide antibodies (AEAb) of the IgG and IgM types by DOT immunobinding assay in the sera of patients suffering from various arteriosclerotic diseases. In total 232 control and pathological sera were studied. In obliterative arteriosclerosis of the legs 90%, ischemic heart disease 67% and hypertension 60% of sera were positive for AEAb of the IgG type independent of age. In the case of diabetes mellitus, however, the duration of the disease was determinant. In rheumatoid arthritis, the results were negative. No clear-cut positivity could be demonstrated in stroke patients either. These results indicate that AEAb can be detected in some diseases and DOT appears to be an appropriate method for the AEAb screening in various diseases.

Topics: Adult; Age Factors; Aged; Arteriosclerosis; Arthritis, Rheumatoid; Coronary Disease; Diabetes Mellitus; Elastin; Female; Humans; Hypertension; Immunoglobulin G; Immunoglobulin M; Immunosorbent Techniques; Male; Middle Aged; Peptide Fragments

Topics: Animals; Diabetes Mellitus; Elastin; Extracellular Matrix; Fibronectins; Homeostasis; Humans

Glucose inhibits collagen fibril formation in vitro. A linear dose response was observed, with half-maximum inhibition of fibril formation occurring at 50 mM glucose. Nonfibrillar collagen cannot be cross-linked by lysyl oxidase, an enzyme that catalyzes the initial cross-linking reaction. The degree of decreased fibril formation correlated with the loss of ability of the collagen to serve as a substrate for lysyl oxidase. Collagen that is not cross-linked is unstable and more susceptible to collagenolytic attack. Interference with collagen cross-linking and more rapid degradation may explain the decreased amounts of interstitial collagen and the poor healing of wounds associated with diabetes mellitus.

Topics: Animals; Collagen; Diabetes Mellitus; Diabetes Mellitus, Experimental; Elastin; Glucose; Humans; In Vitro Techniques; Macromolecular Substances; Protein Conformation; Protein-Lysine 6-Oxidase; Rats

The alteration of the structural organization of dermal connective tissue was studied by light and electron microscopy and by biochemical techniques in normal human and in diabetic patients using skin biopsies. Part of the tissue was used for light and electron microscopy, the rest was incubated in the presence of 3H-lysine for four hours. The 3H-lysine labelled biopsies were submitted to a sequential extraction procedure in order to obtain representative macromolecular fractions containing the matrix macromolecules. The extracts were analyzed for their chemical composition and radioactivity. Electron microscopy revealed ultrastructural modifications of the fibroblasts, of the collagen and elastic fibers in the diabetic dermis. Fibroblasts contained an increased amount of electron dense deposits in the cytoplasm and dilated endoplasmic reticulum. The collagen bundles were dissociated. Elastic fibers under the epithelial basal laminae were fragmented or absent. The incorporation pattern of 3H-lysine into these macromolecular fractions was different in the normal and diabetic skin biopsies. The percentage of total radioactivity incorporated increased significantly in the 1M CaCl2 extractable fraction an in the 6M urea extractable fraction and decreased significantly in the collagenase and elastase extracts in diabetic skin biopsy. These results demonstrate the existence of morphological and biochemical alterations in diabetic connective tissue (dermis) reflecting alterations in the relative rates of synthesis and/or degradation of the intercellular matrix macromolecules as well as of their microarchitectural arrangement.

Topics: Adolescent; Adult; Aging; Biopsy; Buffers; Calcium Chloride; Child; Collagen; Cytoplasm; Diabetes Mellitus; Elastin; Endoplasmic Reticulum; Fibroblasts; Glycoproteins; Humans; Hydroxyproline; Intercellular Junctions; Lysine; Microbial Collagenase; Pancreatic Elastase; Skin; Tritium; Urea

Topics: Aorta; Arteriosclerosis; Collagen; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Elastin; Humans

Histochemical investigations on elastic membranes of vessels under normally and diabetic conditions have been accomplished. These studies were made on man (diabetic and non-diabetic subjects) and on rats with streptozotocin-diabetes. The results are comparable among one another. The amino acids histidine, tyrosine and tryptophan were not demonstrable. The detection of primary NH2-groups (ninhydrin-Schiff-method and o-diacetylbenzen-reaction) was positive however. The results of the reactions in healthy men and animals were more distinct than in diabetic human subjects and animals. In healthy children the intensities of the histochemically reactions were higher than in adults.

Topics: Adult; Age Factors; Amino Acids; Animals; Arteries; Child; Diabetes Mellitus; Diabetic Angiopathies; Elastic Tissue; Elastin; Histidine; Histocytochemistry; Humans; Rats; Streptozocin; Tryptophan; Tyrosine

Topics: Abdomen; Adolescent; Adult; Aged; Biopsy; Child; Diabetes Mellitus; Ear; Elastic Tissue; Elastin; Forearm; Humans; Infant, Newborn; Middle Aged