elastin and Chronic-Disease

Disturbances in bone and mineral metabolism in patients with chronic kidney disease (CKD) affect not only the bone diseases but also other organ disorders in the whole body and deteriorate the survival of these patients. The term CKD-Mineral and Bone Disorder (CKD-MBD) has been established describing a broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to CKD. Vascular calcification and secondary hyperparathyroidism are major diseases in CKD-MBD.

Topics: Apoptosis; Bone Density; Bone Diseases, Metabolic; Calcinosis; Chronic Disease; Elastin; Humans; Hyperparathyroidism, Secondary; Kidney Diseases; Muscle, Smooth, Vascular; Receptors, Calcitriol; Receptors, Calcium-Sensing; Vascular Diseases

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

Chronic intermittent hypoxia (CIH) is a major determinant of the cardiovascular morbidity associated with obstructive sleep apnoea (OSA), and the magnitude of CIH impact may be influenced by ageing. Here, we assessed the role of ageing in the early cardiovascular structural remodelling induced by severe CIH in a murine model of OSA.. Early vascular remodelling was observed in young mice exposed to CIH as illustrated by intima-media thickening (mean change: 4.6 ± 2.6 μm; P = 0.02), elastin fibre disorganization (mean change: 9.2 ± 4.5%; P = 0.02) and fragmentation (mean change: 2.5 ± 0.8%; P = 0.03), and collagen (mean change: 3.2 ± 0.6%; P = 0.001) and mucopolysaccharide accumulation (mean change: 2.4 ± 0.8%; P = 0.01). In contrast, vascular remodelling was not apparent in aged mice exposed to CIH. Furthermore, left ventricular perivascular fibrosis (mean change: 0.71 ± 0.1; P < 0.001) and hypertrophy (mean change: 0.17 ± 0.1; P = 0.038) were increased by CIH exposure in young mice, but not in aged mice. Principal component analysis identified similar cardiovascular alterations among the young mice exposed to CIH and both older mouse groups, suggesting that CIH induces premature cardiovascular senescence.. Cardiovascular remodelling induced by severe CIH is affected by the age at which CIH onset occurs, suggesting that the deleterious cardiovascular effects associated with CIH may be more pronounced in younger populations, and such changes resemble chronological age-related declines in cardiovascular structural integrity.

Topics: Age Factors; Aging; Animals; Chronic Disease; Collagen; Disease Models, Animal; Elastin; Female; Glycosaminoglycans; Hypoxia; Mice; Mice, Inbred C57BL; Sleep Apnea, Obstructive; Tunica Intima; Vascular Remodeling

Cyanogenic glycosides are found in a diverse group of plants and are metabolized into thiocyanate by the intestines and liver. Conversion of plant derived thiocyanates into cyanide and isocyanic acid occurs by the activity of neutrophil-derived enzyme myeloperoxidase. Therefore, increased intake of cyanogenic glycoside rich plant based diet may lead to increased isocyanic acid induced protein carbamylation in chronic inflammatory states (increased myeloperoxidase activity). As there is a close relationship between non-enzymatic post-translational modification and protein function, carbamylation induced structural changes also affect the functions of proteins. Carbamylation induced structural alterations of proteins have recently drawn a great attention in the current literature, especially regarding the alterations of proteins with long half-life such as type I collagen, elastin, α-crystallin. We hypothesize that a plant-based natural diet, rich in cyanogenic glycosides, may have unintended consequences on native protein structure/function in individuals with chronic inflammatory diseases such as chronic kidney and rheumatological diseases because of the higher rate of transformation of plant derived thiocyanates into isocyanic acid by the increased activity of neutrophil-derived enzyme myeloperoxidase. Regulation of myeloperoxidase activity or moderation of cyanogenic glycoside rich diet might be important in the prevention/modulation of dangerous protein carbamylation process, especially in this patient group.

Topics: Chronic Disease; Collagen; Cyanates; Cyanides; Diet; Elastin; Glycosides; Humans; Inflammation; Intestines; Liver; Models, Theoretical; Neutrophils; Peroxidase; Protein Carbamylation; Proteins; Risk; Up-Regulation

Arterial stiffness and wave reflection are important components of the ventricular afterload. Therefore, we aimed to assess the arterial wave characteristics and mechanical properties of the proximal pulmonary arteries (PAs) in the hypoxic pulmonary hypertensive rat model. After 21 days in normoxic or hypoxic chambers (24 animals/group), animals underwent transthoracic echocardiography and PA catheterization with a dual-tipped pressure and Doppler flow sensor wire. Wave intensity analysis was performed. Artery rings obtained from the pulmonary trunk, right and left PAs, and aorta were subjected to a tensile test to rupture. Collagen and elastin content were determined. In hypoxic rats, proximal PA wall thickness, collagen content, tensile strength per unit collagen, maximal elastic modulus, and wall viscosity increased, whereas the elastin-to-collagen ratio and arterial distensibility decreased. Arterial pulse wave velocity was also increased, and the increase was more prominent in vivo than ex vivo. Wave intensity was similar in hypoxic and normoxic animals with negligible wave reflection. In contrast, the aortic maximal elastic modulus remained unchanged, whereas wall viscosity decreased. In conclusion, there was no evidence of altered arterial wave propagation in proximal PAs of hypoxic rats while the extracellular matrix protein composition was altered and collagen tensile strength increased. This was accompanied by altered mechanical properties in vivo and ex vivo. NEW & NOTEWORTHY In rats exposed to chronic hypoxia, we have shown that pulse wave velocity in the proximal pulmonary arteries increased and pressure dependence of the pulse wave velocity was steeper in vivo than ex vivo leading to a more prominent increase in vivo.

Topics: Animals; Aorta; Arterial Pressure; Biomechanical Phenomena; Chronic Disease; Collagen; Disease Models, Animal; Elastic Modulus; Elastin; Hypertension, Pulmonary; Hypoxia; Male; Models, Cardiovascular; Pulmonary Artery; Pulse Wave Analysis; Rats, Sprague-Dawley; Tensile Strength; Time Factors; Vascular Remodeling; Vascular Stiffness; Viscosity

The ultrastructure of venous valves and walls in chronic venous disease was investigated.. Consecutive patients were categorised into one of three groups (group A: patients with C1 venous disease in accordance with CEAP (Clinical severity, Etiology, Anatomy, Pathophysiology); group B: C2 and C3; group C: C4, C5 and C6). The terminal or preterminal valve and adjacent vessel wall was harvested from the great saphenous vein. Sections were examined with a transmission electron microscope. The volumes of elastin and of collagen per unit surface area of valve were assessed, as well as the surface endothelium of valve and vessel wall.. The study population consisted of 17 patients. The elastin ratio was analysed by means of stereology. Mean values were: in group A, 0.45 μm3/m2; in group B, 0.67 μm3/m2; in group C, 0.97 μm3/m2. The ratio was similar for collagen (A, 15.7 μm3/m2; B, 26.8 μm3/m2; C, 30.1 μm3/m2). Surface analysis of the valve endothelium and the adjacent vessel wall endothelium showed a trend towards increasing damage with more severe disease.. With progression of venous disease, the valve elastin content, assessed morphologically, seems to increase, and the endothelium of the venous valve and the vein wall tend to show more damage.

Topics: Adult; Aged; Biomarkers; Chronic Disease; Collagen; Disease Progression; Elastin; Endothelium, Vascular; Female; Humans; Male; Microscopy, Electron, Transmission; Middle Aged; Saphenous Vein; Single-Blind Method; Varicose Veins; Venous Valves

A major feature of chronic wounds is the loss of tissue, with the exposure of dermal components preventing primary closure and leading to bacterial colonization. Bacterial colonization has been proposed as one of the common underlying pathologies present in chronic wounds. The objective of this exploratory study was to identify bacteria cultured from chronic venous leg ulcers and test for proteolytic activity that degrades matrix substrates.. Bacteria were isolated, cultured, and identified from six subjects (average age = 62.8 years) over 2-10 months under an approved protocol using swabs and microbiological culture media. Proteolytic activity against (a) gelatin, (b) an elastin substrate, and (c) a serine/trypsin-sensitive substrate was determined using a colorimetric plate assay with an ELISA plate reader and zymography.. We identified 13 bacteria that expressed proteolytic activity against one or more of the tested substrates. Of these, six were Gram-positive (Staphylococcus aureus, Enterococcus faecalis, Staphylococcus epidermidis, Streptococcus agalactiae, Corynebacterium, and Streptococcus bovis) and seven were Gram-negative (Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Morganella morganii, Klebsiella pneumoniae, Bacteroides fragilis, and Serratia marcescens) organisms. Two of these, S. aureus and P. aeruginosa, are recognized wound pathogens.. Multiple bacteria species isolated from colonized venous leg ulcers have the capacity to secrete proteases capable of degrading components of the extracellular matrix important for wound healing. Matrix degradation by bacteria may contribute to delays in tissue deposition and repair, suggesting that treatment of chronic wounds should include appropriate management of colonizing bacteria.

Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Elastin; Extracellular Matrix; Gelatin; Gram-Negative Bacteria; Gram-Positive Bacteria; Granulation Tissue; Humans; Leg Ulcer; Male; Microbiological Techniques; Middle Aged; Proteolysis; Skin

Composition changes of extracellular matrix (ECM) can lead to functional disorders of the upper airways (UA). The aim of this study was to systematically measure both the association patterns and the correlation degree between tissue composition parameters in UA inflammatory diseases.. Nasal samples were obtained from patients with chronic rhinosinusitis with (CRS+NP), without nasal polyps (CRS), with post-operative adhesions (S) and normal nasal mucosa (NM). A reproducible semi-quantitative method, which takes epithelial and lamina propria damages into account was applied for haematoxylin and eosin, alpha-smooth muscle actin, reticulin, elastin, laminin and collagen type IV stainings.. The most severe cases of epithelial shedding have been found in a significant higher amount in CRS+NP when compared with NM. The most severe cases of inflammatory reaction were mainly found in CRS+NP. CRS+NP had significantly more severe cases of oedema than NM. Excluding elastin, networks in other ECM proteins were found modified in fibrotic fields but to a lesser extend in oedematous regions in all conditions.. Although non specific, oedema in the lamina propria is a key-feature of CRS+NP, while fibrosis, massively present in CRS and S, affects profoundly the distribution of ECM proteins in these areas.

Topics: Actins; Adolescent; Adult; Chronic Disease; Collagen Type IV; Connective Tissue; Edema; Elastin; Extracellular Matrix Proteins; Female; Fibrosis; Humans; Immunohistochemistry; Laminin; Male; Middle Aged; Nasal Mucosa; Nasal Polyps; Reticulin; Rhinitis; Sinusitis; Young Adult

Topics: Adult; Biopsy; Chronic Disease; Cutis Laxa; Elastin; Extracellular Matrix Proteins; Humans; Male; Mutation; Skin; Urticaria; Young Adult

Vascular calcification is the most important cause of cardiovascular disease in patients with chronic kidney disease (CKD). Medial layer vascular calcification, which is recognized to be an active process (i.e. the transformation of vascular smooth muscle cells into osteoblast-like cells), is common in CKD patients. We have recently reported the possibility of an interaction between elastin degradation and medial layer vascular calcification. Matrix metalloproteinase-2 (MMP-2), which induces the degradation of elastin, has been implicated in the elastic calcification in arteries of dialysis patients; however, the precise mechanisms by which elastin degradation interacts with the development of vascular calcification remain to be studied. To clarify the mechanisms by which elastin degradation is involved in the development of medial layer vascular calcification in the uremic milieu, we induced aortic medial layer calcification in 5/6 nephrectomized uremic rats (male Sprague-Dawley rats) fed a diet containing high phosphate (1.2%) and lactate (20%). After 10 weeks, the rats were euthanized for the measurement of serum chemistry profiles and histological analyses. The uremic rats showed significant increases in blood pressure, serum creatinine, phosphate, and parathyroid hormone levels compared with normal rats. Von Kossa staining showed medial layer aortic calcification in the uremic rats. In calcified lesions, thin elastic lamellae were observed by elastin staining, indicating that elastin degradation could occur in the area. Furthermore, MMP-2 expression determined by immunohistochemistry was also observed in the same area. Elastin degradation accompanied by MMP-2 expression might be involved in the development of medial layer vascular calcification in uremic rats.

Topics: Animals; Aorta; Blood Pressure; Calcinosis; Cardiovascular Diseases; Chronic Disease; Creatinine; Elastin; Kidney Diseases; Male; Matrix Metalloproteinase 2; Parathyroid Hormone; Phosphates; Rats; Rats, Sprague-Dawley; Uremia

In the present study we tested the hypothesis whether hyperhomocysteinemia, an elevated homocysteine level, induces venous phenotype in artery. To test our hypothesis, we employed wild type (WT) and cystathionine β-synthase heterozygous (+/-) (CBS+/-) mice treatment with or without folic acid (FA). Aortic blood flow and velocity were significantly lower in CBS+/-mice compared to WT. Aortic lumen diameter was significantly decreased in CBS+/-mice, whereas FA treatment normalized it. Medial thickness and collagen were significantly increased in CBS+/-aorta, whereas elastin/collagen ratio was significantly decreased. Superoxide and gelatinase activity was significantly high in CBS+/-aorta vs WT. Western blot showed significant increase in MMP-2, -9,-12, TIMP-2 and decrease in TIMP-4 in aorta. RT-PCR revealed significant increase of vena cava marker EphB4, MMP-13 and TIMP-3 in aorta. We summarize that chronic HHcy causes vascular remodelling that transduces changes in vascular wall in a way that artery expresses vein phenotype.

Topics: Animals; Aorta; Blotting, Western; Chronic Disease; Collagen; Cystathionine beta-Synthase; Elastin; Ephrin-B2; Folic Acid; Gene Expression; Genotype; Hemorheology; Hyperhomocysteinemia; Male; Matrix Metalloproteinases; Mice; Mice, Transgenic; Phenotype; Receptor, EphB4; Tissue Inhibitor of Metalloproteinase-2; Tissue Inhibitor of Metalloproteinase-4; Tissue Inhibitor of Metalloproteinases; Tunica Intima; Veins

Neonatal chronic lung disease is characterized by failed formation of alveoli and capillaries, and excessive deposition of matrix elastin, which are linked to lengthy mechanical ventilation (MV) with O(2)-rich gas. Vitamin A supplementation has improved respiratory outcome of premature infants, but there is little information about the structural and molecular manifestations in the lung that occur with vitamin A treatment. We hypothesized that vitamin A supplementation during prolonged MV, without confounding by antenatal steroid treatment, would improve alveolar secondary septation, decrease thickness of the mesenchymal tissue cores between distal air space walls, and increase alveolar capillary growth. We further hypothesized that these structural advancements would be associated with modulated expression of tropoelastin and deposition of matrix elastin, phosphorylated Smad2 (pSmad2), cleaved caspase 3, proliferating cell nuclear antigen (PCNA), VEGF, VEGF-R2, and midkine in the parenchyma of the immature lung. Eight preterm lambs (125 days' gestation, term approximately 150 days) were managed by MV for 3 wk: four were treated with daily intramuscular Aquasol A (vitamin A), 5,000 IU/kg, starting at birth; four received vehicle alone. Postmortem lung assays included quantitative RT-PCR and in situ hybridization, immunoblot and immunohistochemistry, and morphometry and stereology. Daily vitamin A supplementation increased alveolar secondary septation, decreased thickness of the mesenchymal tissue cores between the distal air space walls, and increased alveolar capillary growth. Associated molecular changes were less tropoelastin mRNA expression, matrix elastin deposition, pSmad2, and PCNA protein localization in the mesenchymal tissue core of the distal air space walls. On the other hand, mRNA expression and protein abundance of VEGF, VEGF-R2, midkine, and cleaved caspase 3 were increased. We conclude that vitamin A treatment partially improves lung development in chronically ventilated preterm neonates by modulating expression of tropoelastin, deposition of elastin, and expression of vascular growth factors.

Topics: Animals; Animals, Newborn; Chronic Disease; Dietary Supplements; Elastin; Female; Gestational Age; Lung; Lung Diseases; Pregnancy; Premature Birth; Pulmonary Alveoli; Pulmonary Gas Exchange; Respiration, Artificial; Sheep; Tropoelastin; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Vitamin A; Vitamins

Hypoxic pulmonary hypertension (HPH) causes extralobar pulmonary artery (PA) stiffening, which potentially impairs right ventricular systolic function. Changes in the extracellular matrix proteins collagen and elastin have been suggested to contribute to this arterial stiffening. We hypothesized that vascular collagen accumulation is a major cause of extralobar PA stiffening in HPH and tested our hypothesis with transgenic mice that synthesize collagen type I resistant to collagenase degradation (Col1a1(R/R)). These mice and littermate controls that have normal collagen degradation (Col1a1(+/+)) were exposed to hypoxia for 10 days; some were allowed to recover for 32 days. In vivo PA pressure and isolated PA mechanical properties and collagen and elastin content were measured for all groups. Vasoactive studies were also performed with U-46619, Y-27632, or calcium- and magnesium-free medium. Pulmonary hypertension occurred in both mouse strains due to chronic hypoxia and resolved with recovery. HPH caused significant PA mechanical changes in both mouse strains: circumferential stretch decreased, and mid-to-high-strain circumferential elastic modulus increased (P < 0.05 for both). Impaired collagen type I degradation prevented a return to baseline mechanical properties with recovery and, in fact, led to an increase in the low and mid-to-high-strain moduli compared with hypoxia (P < 0.05 for both). Significant changes in collagen content were found, which tended to follow changes in mid-to-high-strain elastic modulus. No significant changes in elastin content or vasoactivity were observed. Our results demonstrate that collagen content is important to extralobar PA stiffening caused by chronic hypoxia.

Topics: Animals; Biomechanical Phenomena; Blood Pressure; Chronic Disease; Collagen Type I; Collagen Type I, alpha 1 Chain; Disease Models, Animal; Elastic Modulus; Elastin; Hydroxyproline; Hypertension, Pulmonary; Hypoxia; Mechanotransduction, Cellular; Mice; Mice, Transgenic; Mutation; Pulmonary Artery; Recovery of Function; Time Factors; Vasoconstriction; Vasoconstrictor Agents

The potential role of elastin in patients with myeloid leukemia treated with hematopoietic stem cell transplantation (HSCT) has not been investigated so far. The objective of the study was to evaluate elastin metabolism before and at two time-points after HSCT.. Forty patients (22 male and 18 female, median age: 34 years, range: 14-54) were included. The diagnoses were acute myeloid leukemia (AML, n=25) and chronic myeloid leukemia (CML, n=15). Busulfan and cyclophosphamide (4+2) were administered as conditioning. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. Twenty-three patients experienced acute GVHD and 17 developed chronic GVHD. Plasma elastase activity (EA) and plasma elastin-derived peptide concentration (EDPc) were measured.. There were statistically significant differences in EA before HSCT (1.3 U/ml) compared with day +30 (2.9 U/ml) and day +100 (3.2 U/ml) after HSCT (p<0.001 for both). EA was also higher in patients with chronic GVHD than in those who did not develop chronic GVHD. EDPc was significantly higher on days +30 (49.3 U/ml) and +100 (57.7 U/ml) after HSCT than on day -10 before HSCT (15.5 U/ml, p<0.001 for both). EDPc was significantly higher in patients with chronic GVHD.. EA and EDPc were increased in patients after HSCT. If the role of elastase in the pathogenesis of GVHD is confirmed, it will be possible to apply inhibitors of elastases in the treatment of this condition in the near future.

Topics: Acute Disease; Adolescent; Adult; Chronic Disease; Elastin; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid; Male; Middle Aged; Pancreatic Elastase; Peptide Fragments; Transplantation, Homologous; Young Adult

Despite extensive strides in understanding pressure overload induced heart failure, there is very little known about oxidative stress induced matrix metalloproteinase (MMP) activation, collagen degradation and remodeling in pressure overload heart failure. We hypothesize that pressure overload leads to redox imbalance causing increased expression/activity of MMP-2/9 producing collagen degradation and heart failure. To test this hypothesis, we created pressure overload heart failure by abdominal aortic stenosis (AS) in wild-type C57BL/6J and collagen mutant (Col1a1 with 129 s background) mice. At 4 weeks, post surgery, functional parameters were measured. Left ventricle (LV) tissue sections were analyzed by histology, Western Blot and PCR. The results suggest an increase in iNOS with a decrease in eNOS, an increase in nitrated protein modification and depletion of antioxidants thioredoxin and SOD in pressure overload. MMP-2/9 expression/activity and collagen degradation were increased in the AS animals. To determine whether a mutation in the collagen gene at the site of MMP cleavage mitigates cardiac hypertrophy, we used Col1a1 mice. In these mice, the AS induced LV hypertrophy (LVH) was ameliorated. In conclusion, our results suggest that AS leads to increased oxidative stress, expression/activity of MMP-2/9 and a decrease in antioxidant expression producing collagen degradation and heart failure.

Topics: Analysis of Variance; Animals; Aortic Valve Stenosis; Blood Pressure; Blotting, Western; Chronic Disease; Collagen; Disease Models, Animal; Echocardiography; Elastin; Electrocardiography; Enzyme Activation; Heart Failure; Hypertrophy, Left Ventricular; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Research Design; Reverse Transcriptase Polymerase Chain Reaction; Stroke Volume; Ventricular Dysfunction, Left

Early diagnosis and monitoring progression of chronic diseases in elastin-rich tissues, such as chronic progressive lymphoedema in draught horses and chronic obstructive pulmonary disease (COPD) is still a real challenge in the horse. Use of an enzyme-linked immunosorbent assay (ELISA) to detect anti-elastin antibody (AEAb) levels might be useful to assess the status of such diseases. Baseline levels, representing physiological breakdown of elastin in normal horses, are not available at present.. Levels of AEAb in healthy horses are generally low and follow the same age-related pattern as found in man. Therefore, elevation of AEAb levels in serum can be used to evaluate pathological elastin breakdown in elastin-rich tissues.. Sera of 84 clinically healthy Warmblood horses were evaluated for the presence of AEAbs by means of a modified version of an ELISA technique used in man. The horses were divided in 5 age groups: A) < 4 months; B) 4-23 months; C) 2-3 years; D) 4-10 years; and E) > 11 years.. Antibodies to elastin were found in all equine serum samples tested. Their levels were lowest in Group A, low in Groups B and E and highest in animals age 2-10 years.. Measuring AEAbs in serum of horses by an ELISA technique proved to be possible and levels were stable during well-defined life stages.. Changes in AEAb levels are expected to be useful for early diagnosis and for monitoring progression of diseases that affect elastin-rich tissues, such as chronic progressive lymphoedema and COPD.

Topics: Aging; Animals; Autoantibodies; Chronic Disease; Diagnosis, Differential; Disease Progression; Elastin; Enzyme-Linked Immunosorbent Assay; Horse Diseases; Horses; Lung Diseases, Obstructive; Lymphedema; Peptides; Reference Values; Sensitivity and Specificity; Severity of Illness Index

Chronic progressive lymphoedema (CPL) is a recently recognised disease of the lymphatic system characterised by lesions in the skin of the lower legs in several draught horse breeds, including the Belgian Draught hourse. Clinical signs slowly progress and result in severe disfigurement of the limbs. Ideally, supportive treatment should be started early in the disease process. However early diagnosis and monitoring progression of CPL is still a challenge.. Elastin changes, characterised by morphological alterations as well as increased desmosine levels, in the skin of the distal limbs of horses affected with CPL are probably associated with a marked release of elastin degradation products, which elicit production of circulating anti-elastin antibodies (AEAbs) in the serum. An enzyme-linked immunosorbent assay (ELISA) for detection of serum AEAbs may document elastin breakdown.. An ELISA technique was used to evaluate levels of AEAbs in sera of 97 affected Belgian Draught horses that were clinically healthy except for possible skin lesions, associated with CPL in their distal limbs. The horses were divided into 5 groups according to the severity of these skin lesions: normal horses (Group 1, n = 36), horses with mild lesions (Group 2, n = 43), horses with moderate lesions (Group 3, n = 8), horses with severe lesions (Group 4, n = 10) and, as a control, healthy Warmblood horses, unaffected by the disease (Group 5, n = 83).. Horses with clinical signs of CPL had significantly higher AEAb levels compared to clinically normal Belgian Draught horses and to healthy Warmblood horses. These levels correlated with severity of lesions.. CPL in draught horses is associated with an increase of serum AEAbs.. Evaluation of serum levels of AEAbs by ELISA might be a useful diagnostic aid for CPL. Pathological degradation of elastic fibres, resulting in deficient support of the distal lymphatics, is proposed as a contributing factor for CPL in Belgian Draught horses.

Topics: Aging; Animals; Autoantibodies; Breeding; Chronic Disease; Desmosine; Diagnosis, Differential; Disease Progression; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Horse Diseases; Horses; Lymphedema; Male; Peptides; Sensitivity and Specificity; Skin

Nitric oxide (NO) serves multiple functions in the developing lung, and pulmonary NO production is decreased in a baboon model of chronic lung disease (CLD) after premature birth at 125 days (d) gestation (term = 185d). To determine whether postnatal NO administration alters the genesis of CLD, the effects of inhaled NO (iNO, 5 ppm) were assessed in the baboon model over 14d. iNO caused a decrease in pulmonary artery pressure in the first 2d and a greater rate of spontaneous closure of the ductus arteriosus, and lung compliance was greater and expiratory resistance was improved during the first week. With iNO, postmortem pressure-volume curves were shifted upward, lung DNA content and cell proliferation were increased, and lung growth was preserved to equal that which occurs during the same period in utero. In addition, the excessive elastin deposition characteristic of CLD was normalized by iNO, and there was evidence of stimulation of secondary crest development. Thus, in the baboon model of CLD, iNO improves early pulmonary function and alters lung growth and extracellular matrix deposition. As such, NO biosynthetic pathway dysfunction may contribute to the pathogenesis of CLD.

Topics: Administration, Inhalation; Animals; Animals, Newborn; Bronchodilator Agents; Chronic Disease; Elastin; Hemodynamics; Image Processing, Computer-Assisted; Lung; Lung Diseases; Nitric Oxide; Organ Size; Papio; Pulmonary Alveoli; Pulmonary Artery; Pulmonary Circulation

The purpose of the current study was to assess the histologic and rheologic properties of the scarred vocal fold lamina propria during a chronic phase of wound repair in a rabbit model. Eighteen rabbit larynges were scarred using a procedure that involved stripping the vocal fold lamina propria down to the thyroarytenoid muscle, using 3-mm microforceps. The approximate dimension of injury to the vocal fold was 3 x 1.5 x 0.5 mm [length x width x depth]. At 6 months postoperatively, histologic analysis of the scarred and control lamina propria in eight of these rabbits was completed for collagen, procollagen, elastin, and hyaluronic acid. Compared with control samples, scarred tissue samples revealed fragmented and disorganized elastin fibers. Additionally, collagen was significantly increased, organized, and formed thick bundles in the scarred vocal fold lamina propria. Measurements of the viscoelastic shear properties of the scarred and control lamina propria in the remaining 10 rabbits revealed increased elastic shear modulus (G') in 8 of 10 scarred samples and increased dynamic viscosity (eta') in 9 of 10 scarred samples. Although rheologic differences were not statistically significant, they revealed that on average, scarred samples were stiffer and more viscous than the normal controls. Histologic data are interpreted as indicating that by 6 months postinjury, the scarred rabbit vocal fold has reached a mature phase of wound repair, characterized by an increased, organized, and thick bundle collagen matrix. Rheologic data are interpreted as providing support for the potential role of increased, thick bundle collagen, and a disorganized elastin network on shear stiffness and dynamic viscosity in the chronic vocal fold scar. Based on these results, a 6-month postoperative time frame is proposed for future studies of chronic vocal fold scarring using the rabbit animal model.

Topics: Animals; Chronic Disease; Cicatrix; Collagen; Disease Models, Animal; Elastin; Hyaluronic Acid; Image Processing, Computer-Assisted; Immunohistochemistry; Male; Procollagen; Rabbits; Rheology; Viscosity; Vocal Cords; Wound Healing

Intimal hyperplasia is one of the main responses of the vascular wall to injury. In the current study, we tested the hypothesis that endoluminal seeding of host syngeneic vascular cells could limit intimal hyperplasia induced by either mechanical deendothelialization or chronic allograft rejection in rat aorta.. An experimental model of in situ seeding of syngeneic endothelial cells, smooth muscle cells (SMCs), and fibroblasts (FIBs) was used in mechanically deendothelialized and allografted aortas. In a preliminary study, the ability of the three cell types (n = 5 per group) to seed on the deendothelialized luminal surface of the aortic wall was evaluated after 2 days, with the use of fluorescent PKH as marker. In the first model, the abdominal aorta of Lewis rats was deendothelialized (n = 6) or deendothelialized and seeded with either SMCs (n = 6) or FIBs (n = 6) before flow was restored. In the allograft model, aortas were harvested from dark agouti rats and orthotopically grafted in Lewis receivers, directly (n = 6) or after deendothelialization. Deendothelialization was performed alone (n = 6) or associated with the seeding of similar host (Lewis) syngeneic SMCs (n = 6) or FIBs (n = 6). Results were evaluated at 2 months with histologic and morphometric methods.. SMCs and FIBs were able to adhere in situ to the deendothelialized aortic wall, whereas endothelial cells were not. In mechanically deendothelialized aortas, the seeding of syngeneic SMCs led to a significant reduction in intimal thickness compared with deendothelialized aortas or FIB-seeded aortas (26.9 +/- 1.7 microm vs 55.5 +/- 1.7 and 56.7 +/- 1.7 microm, respectively), and a lower nuclear content (382.2 +/- 35.7 microm(2) vs 779.6 +/- 65.9 and 529.6 +/- 24.3 microm(2), respectively) of neointima. After SMC seeding, intimal hyperplasia was richer in elastin, whereas after FIB seeding it was richer in collagen. In allografts, the seeding of syngeneic SMC led to a significant reduction in intimal thickness compared with control aortas, deendothelialized aortas, or FIB-seeded aortas (31.6 +/- 1.1 microm vs 88.55 +/- 2.8, 74.6 +/- 2.9, and 85.7 +/- 2.6 microm, respectively), and a reduced nuclear content of the neointima (444.9 +/- 23.4 microm(2) vs 1529.1 +/- 116, 972.3 +/- 50, and 645.2 +/- 32.4 microm(2), respectively). Differences observed in the extracellular matrix composition were equivalent to those observed in the mechanically deendothelialized model.. Our results suggest that endoluminal seeding of syngeneic SMCs can be effective in reducing intimal hyperplasia both in a deendothelialization model and in arterial allografts. SMC and FIB endoluminal seeding led to a significatively different accumulation of extracellular matrix in the intima.

Topics: Analysis of Variance; Animals; Aorta, Abdominal; Cell Adhesion; Cell Division; Cell Movement; Chronic Disease; Collagen; Disease Models, Animal; Elastin; Fibroblasts; Graft Rejection; Hyperplasia; Inflammation; Male; Muscle, Smooth, Vascular; Rats; Rats, Inbred Lew; Rats, Inbred Strains; Time Factors; Transplantation, Homologous; Transplantation, Isogeneic; Tunica Intima; Wound Healing

Recent data indicate that extracellular matrix (ECM) proteins can provide costimulatory signals during the process of T cell activation. Those proteins accumulate in situ during allograft rejection; therefore, it may be expected that local ECM: T cell interactions may be relevant in the immunopathology of rejection. T cell adhesion from allograft of recipients with stable renal function (RAR-S) and patients with biopsy-proven chronic rejection (RAR-CH) to ECM proteins (collagen type IV, fibronectin, elastin) was measured. Furthermore, T cell: endothelial interactions in vitro were studied. Adhesion of PHA-activated T cells from both groups of allograft recipients to fibronectin, collagen type IV and elastin was significantly lower than in healthy blood donors. Moreover, similar pattern of activity was observed when T cell attachment to resting and activated endothelium was studied. There were no significant differences in the number of circulating CD45RO and CD4 positive T cells. We observed a higher (although not significantly) adhesion of the T cells to resting human dermal microvascular endothelial cells (HMEC) in the chronic stages of rejection, which can suggest that the immunosuppressive protocol used in the treatment of chronic rejection is insufficient to control immunopathologic phenomena occurring in that process. Therefore, it may be argued that too low immunosuppression can be one of the factors responsible for the development of this complication.

Topics: Cell Adhesion; Chronic Disease; Collagen; Elastin; Endothelium, Vascular; Extracellular Matrix Proteins; Female; Fibronectins; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Lymphocyte Activation; Male; T-Lymphocytes; Transplantation, Homologous

To investigate (i) elastin degradation and the possible association between proteolysis and inflammation in abdominal aortic aneurysm disease (AAA), and (ii) the presence of cytomegalovirus (CMV) infection in the walls of AAA.. Specimens from 12 infrarenal AAAs, eight aortas with occlusive disease (AOD) and two normal aortas were studied by conventional light microscopy, immunohistochemistry using a monoclonal anti-elastin antibody BA-4 and anti-CMV antibody and transmission electron microscopy (TEM).. In AAA the decrease in elastin immunoreactivity and the presence of elastin degradation was associated with increased mononuclear inflammatory cell infiltrates (p = 0.004 and p = 0.00002, respectively). The CMV immunostainings of the normal aortic wall and all the AAA and AOD samples were negative, nor could any CMV particles be demonstrated by TEM.. The chronic inflammation and degradation of elastin in AAA suggests a possible immune-mediated mechanism. The inflammation may be induced by the chemotactic properties of elastin-derived peptides.

Topics: Adult; Aged; Antigens, Viral; Aortic Aneurysm, Abdominal; B-Lymphocytes; Chronic Disease; Cytomegalovirus Infections; Elastin; Female; Humans; Immunohistochemistry; Immunophenotyping; Inflammation; Macrophages; Male; Microscopy, Electron; Middle Aged; T-Lymphocytes

A 31-year-old man had cutis laxa after an urticarial eruption. He had no systemic manifestations. In urticarial lesions, elastolysis occurred only within the inflammatory infiltrate of neutrophils around the vessels and between the collagen bundles. In lax skin, elastolysis occurred throughout the entire dermis. Electron microscopic study showed a markedly decreased number of elastic fibers, with elastolysis most predominant near the inflammatory cells. These findings suggest that the neutrophil plays a significant role in the destruction of elastic fibers and subsequent development of cutis laxa.

Topics: Adult; Biopsy; Chronic Disease; Cutis Laxa; Elastic Tissue; Elastin; Epidermis; Fibroblasts; Humans; Male; Microscopy, Electron; Neck; Skin; Thorax; Urticaria

An elastin peptide (kE57) obtained from organoalkaline hydrolysis of calf ligamentum nuchae insoluble elastin, was isolated by gel permeation on Sephadex G150 and high performance liquid chromatography on a TSK G 3000 SW column. It possessed an average Mr = 57,000 and similar amino acids composition as its insoluble counterpart. kE57 behave as a competitive inhibitor of human neutrophil elastase (HNE) with Ki = 1.4 microM; it also inhibited porcine pancreatic elastase (PPE) but less efficiently Ki = 180 microM. Identification of elastic fibres in rat gingiva was ascertained by light and electron microscopic studies. Morphometric studies indicated that rat gingiva contained similar levels of elastic fibres (= 2%) as human skin; elastic fibres networks from both tissues also displayed high structural analogy. Gingival chronic inflammation was induced in rats by mechanical impaction associated with an hyperglucidic diet. After 5 weeks, the levels of rat gingiva elastic fibres, decreased from Vv = 1.94 +/- 0.1% to Vv = 1.02 +/- 0.06%. Local injections of kE57: 100 micrograms per day, 5 days a week for 5 weeks did restore the integrity of the gingiva elastic fibres network: Vv = 1.84 +/- 0.1. Without influencing leucocyte infiltration, it is proposed that elastin-derived peptides, acting as potent competitive inhibitor of neutrophil elastase involved in periodontitis, might be of therapeutic value.

Topics: Animals; Cattle; Chronic Disease; Connective Tissue; Disease Models, Animal; Elastic Tissue; Elastin; Gingivitis; Humans; Leukocyte Elastase; Pancreatic Elastase; Peptide Fragments; Rats; Swine

Rats were intoxicated with mercuric chloride (1 mg/kg b.w.) daily, for 12 weeks. An increase of total collagen and elastin content was found in the skin, the lungs, the liver, the kidneys and the heart muscle. The increase resulted from the elevated level of soluble collagen. These changes were accompanied by elevated hydroxyproline level in serum and urine. It is concluded that chronic intoxication with mercury leads to disturbed composition of the connective tissue matrix.

Topics: Animals; Chronic Disease; Collagen; Elastin; Male; Mercuric Chloride; Mercury Poisoning; Rats; Rats, Wistar; Tissue Distribution

Cutaneous aging consists of chronologic aging as well as actinic damage, referred to as photoaging. Most of the morphologic changes associated with an aged appearance result from actinic damage to the skin. The morphologic changes in sun-damaged skin are associated with accumulation of material having the staining characteristics of elastin, known as solar elastosis, in the superficial dermis. Previous studies have demonstrated the presence of elastin within areas of solar elastosis; however, little is known about the mechanisms leading to elastin accumulation in photoaged skin. In addition, fibrillin, the fibrillar component of elastic fibers, has been found in small amounts in solar elastosis. In this study we demonstrate increased elastin mRNA levels in photoaged skin, as well as increased elastin and fibrillin mRNAs in skin explant-derived fibroblasts using Northern hybridizations, compared with controls from sun-protected sites of the same individual. Increased elastin mRNA levels result from transcriptional upregulation of the gene, as demonstrated by transient transfections with a human elastin promoter/chloramphenicol acetyltransferase construct. Elevated mRNA levels were also correlated with increased elastin and fibrillin deposition in paired biopsy specimens from photodamaged and non-sun-exposed skin, as demonstrated by immunohistochemical staining. Thus, approaches to counteract transcriptional activation of elastin gene expression may be useful in preventing the changes associated with cutaneous photoaging.

Topics: Aged; Aging; Blotting, Northern; Cells, Cultured; Chloramphenicol O-Acetyltransferase; Chronic Disease; Elastin; Fibrillins; Gene Expression; Genes, Reporter; Humans; Immunohistochemistry; Male; Microfilament Proteins; Middle Aged; Skin; Sunburn; Transfection

Using light microscopic immunohistochemistry, we studied the immunolocalization and immunoreactivity of the extracellular matrix, including collagen types III, IV, VI, laminin, and alpha elastin in the lamina cribrosa of monkey eyes with normal and experimentally chronic glaucoma. Our results showed: (1) abnormal linearlike immunodeposits of both collagen type IV and laminin in the margin of the lamina cribrosa with significant density in the glaucomatous eyes; (2) the immunoreactivity of collagen type III resembled that of the normal eye, but was slightly stronger at the laminar surface; (3) findings with collagen type VI resembled those of type III with an enhanced linearlike staining surrounding the nerve-fiber bundles. Furthermore, staining of alpha elastin demonstrated dramatic changes in both reactivity and localization. The lamina cribrosa of glaucomatous eyes showed a markedly reduced immunoreactivity as well as an irregular, interrupted pattern. These observations suggest that the changes might be a secondary to the long-standing elevation of intraocular pressure. The alteration of these macromolecules may modify the course of glaucomatous optic damage.

Topics: Animals; Chronic Disease; Collagen; Disease Models, Animal; Elastin; Extracellular Matrix; Fundus Oculi; Glaucoma; Immunoenzyme Techniques; Intraocular Pressure; Laminin; Laser Therapy; Macaca fascicularis; Optic Disk

The progression of structural changes in the pulmonary arterial bed were followed in a model of chronic pulmonary hypertension. Chronically instrumented awake sheep received continuous air embolization for 0 (controls), 1, 4, 8, or 12 days (n = 5-6/group). After the period of embolization, the lungs were removed, the pulmonary arteries were distended with barium-gelatin, and the lungs were fixed via the airways with formal-saline. Quantitative techniques were applied to sections from random blocks from the lungs of each animal. One day of embolization resulted in granulocyte sequestration in the lung interstitium and in small vessels; additionally, intraalveolar and perivascular edema was present. By 4 days, increased medial thickness, appearance of muscle in smaller arteries than normal (e.g., muscular arteries at alveolar duct level: control = 1.2 +/- 1.2%; day 4 = 22.7 +/- 7.7) and reduction in number of barium-filled intraacinar arteries was found. The arterial changes progressed in severity to day 8 and were similar at day 12. Since arterial remodelling involves increased elastin deposition, the concentration of elastin peptides was measured in lung lymph. Increased flux of elastin peptides was apparent from day 2 of embolization and continued to increase to a level 20 x baseline by day 12 (baseline 351 +/- 86 micrograms/15 min; day 12 = 6338 +/- 2999). Comparison of the onset of the structural changes with previous findings shows that the arterial remodelling parallels the onset of sustained pulmonary hypertension. The increase in lung-lymph elastin peptides by day 2 provides evidence that vascular remodelling is initiated before day 4 of embolization. The early sequestration of granulocytes and appearance of edema suggest that these may be part of the trigger to the development of the structural changes.

Topics: Angiography; Animals; Biopsy; Blood Vessels; Cardiomegaly; Chronic Disease; Elastin; Embolism, Air; Hypertension, Pulmonary; Lung; Osmolar Concentration; Peptides; Pulmonary Circulation; Sheep

Cells found in the intima and media of the cranial mesenteric artery of a mature mare with chronic arteritis were identified as smooth muscle cells and occurred in association with collagen and elastin fibres. As no fibroblasts were demonstrable within these regions, the smooth muscle cells were the likely source of the extracellular matrix. In contrast, the abnormal adventitis from the same artery contained abundant fibroblasts which are considered to be the source of the adventitial collagen.

Topics: Animals; Arteritis; Chronic Disease; Collagen; Elastin; Extracellular Matrix; Female; Horses; Mesenteric Arteries; Microscopy, Electron; Muscle, Smooth, Vascular; Strongyle Infections, Equine

We have determined the effect of two elastase-specific synthetic low molecular weight substrates, L-pyroglutamylprolylvaline-paranitroanilide and succinyltrialanyl-paranitroanilide, together with insoluble elastin-fluorescein, on the determination of the neutrophil elastase (NE) inhibitory capacity of purified alpha 1-proteinase inhibitor (alpha 1-PI) and bronchial antileukoprotease (ALP). In addition, the inhibitory capacities of mixtures of alpha 1-proteinase inhibitor, antileukoprotease and alpha 2-macroglobulin prepared in ratios similar to that in lung secretions were determined. Purified inhibitors, alone or in combinations, inhibited about 1 mole neutrophil elastase per mole inhibitor when assessed using synthetic substrates. However, when elastin-fluorescein was used in the assay system, the purified inhibitors showed an inhibitory capacity that was 40-85% of the value obtained using synthetic substrates. Even less inhibition was observed when mixtures of inhibitors were assessed using elastin-fluorescein (23-44% of the value for synthetic substrates). Our data indicate that results of elastase inhibitor activity measurements depend on the type of substrate which has been used.

Topics: alpha 1-Antitrypsin; alpha-Macroglobulins; Blood Proteins; Bronchi; Bronchitis; Chronic Disease; Elastin; Humans; Molecular Weight; Neutrophils; Oligopeptides; Pancreatic Elastase; Protease Inhibitors; Proteinase Inhibitory Proteins, Secretory; Proteins; Pyrrolidonecarboxylic Acid

Prolidase deficiency occurred in two sisters suffering from recurrent leg ulcers that appeared in early childhood. The patients presented the typical clinical symptoms of the disease, including characteristic facies, dermatologic manifestations of the lower extremities, splenomegaly, and hematologic anomalies. Large amounts of iminodipeptides were excreted into the urine, and prolidase activity in their erythrocytes was virtually absent. Changes associated with a connective-tissue disorder were demonstrated by light and electron microscopic studies of the patients' apparently normal skin. Collagen fibers were smaller than in controls and were irregularly packed; the fibrils had normal aspect but were significantly smaller than in one age-matched control. Elastin fibers appeared altered both in size and structure.

Topics: Adult; Chronic Disease; Collagen; Dipeptidases; Elastin; Erythrocytes; Female; Humans; Hydroxyproline; Leg Ulcer; Skin

The qualitative and quantitative characteristic of the connective tissue of aorta of albino rats was followed up, the rats having been treated with phosphororganic pesticide chloracetophon in doses I/20 and I/100 LD50 for six months. With the effect of the lower dose, disturbances were observed, affecting mainly the components of the main intercellular substance--glycoproteins and glycosaminoglycans. The higher dose leads to disturbances in the quality and quantity of the fibrous structures--elastin and collagen on the background of changed ratio sulphated GAG/non-sulphated GAG. The changes observed are an evidence for an accelerated ageing of the vascular aortic wall under the effect of chloracetophon and should be given consideration for its hygienic standardization.

Topics: Animals; Aorta; Chronic Disease; Collagen; Connective Tissue; Dose-Response Relationship, Drug; Elastin; Histocytochemistry; Insecticides; Male; Organophosphorus Compounds; Rats

Female Wistar rats were exposed to CS2 for 13 months. Afterwards collagen and elastin content in aorta and lungs was determined. In addition, collagen and non-collagen protein biosynthesis was determined using 14-C glycine incorporation to proteins. Collagen and elastin content in aorta wall and elastin concentration in lungs were found to be increased. Isotopic method indicated that the specific activity of collagen in aorta wall was increased and activity of pulmonary collagen and non-collagen proteins of aorta and lungs was decreased. The above is indicative of: lowered biosynthesis of noncollagen proteins of aorta and lungs, increased biosynthesis of aorta collagen and increased biosynthesis of aorta and lung elastin. Increased biosynthesis of collagen and elastin in aorta may suggest a possibility of CS2 atherogenic effects.

Topics: Animals; Aorta; Arteriosclerosis; Carbon Disulfide; Chronic Disease; Collagen; Connective Tissue; Elastin; Female; Lung; Rats; Stimulation, Chemical

Topics: Arteries; Chronic Disease; Collagen; Elastic Tissue; Elastin; Hepatitis; Humans; Liver; Liver Cirrhosis; Microscopy, Electron

Topics: Acute Disease; Chronic Disease; Elastin; Fluorometry; Humans; Pancreatic Elastase; Pancreatitis

Topics: Angiography; Animals; Arteries; Chronic Disease; Collagen; Collateral Circulation; Coronary Disease; Coronary Vessels; Dogs; Elastin; Female; Glycosaminoglycans; Histocytochemistry; Male; Mitosis; Regeneration