elastin and Sclerosis

The large and medium-sized arteries in elderly people show varying degrees of intimal and medial change. The medial change is known as age-related medial degeneration and sclerosis (ARMDS). The ARMDS results in systolic hypertension and left ventricular hypertrophy of the heart as a result of loss of arterial elasticity. It also causes aortic dilatation, or even aortic aneurysm. The ARMDS and atherosclerosis are distinct entities, but are often overlapped and confused with each other. The present review mainly focuses on ARMDS and briefly addresses atherosclerosis, and aging of arterioles, capillaries and veins. The smooth muscle cells in the inner half of the aortic media of elderly people degenerate and undergo apoptosis. This causes degradation of elastin fibers and the accumulation of collagen fibers in the media, but the inflammatory infiltrates are scarce. Biochemical studies showed an age-related decrease of elastin and its crosslinks, and an increase of collagen and its crosslink. Because the turnover of elastin is very long, it likely suffers from glycation (Maillard reaction) and glyco-oxidative reaction. The advanced glycation end-products accumulate in the aortic media with increasing age. Alcian-blue positive mucin accumulates in aortic media in elderly people. The major component of the increase of aortic mucin is chondroitin-6-sulfate. Microcalcification is frequent in the inner acellular portion of the aortic media in elderly people. Calcium contents increase with age. In conclusion, the ARMDS is a distinct pathological entity with clinical significance. The pathogenesis of ARMDS is unclear; the mechanical stress of elastin, endothelial dysfunction, and glycation of elastin are proposed.

Topics: Aging; Arterial Occlusive Diseases; Arteries; Atherosclerosis; Capillaries; Collagen; Dilatation, Pathologic; Disease Progression; Elasticity; Elastin; Endothelium, Vascular; Glycation End Products, Advanced; Glycosaminoglycans; Humans; Immunohistochemistry; Microfibrils; Sclerosis; Tunica Media

Topics: Arteries; Arteriosclerosis; Cholesterol; Collagen; Elastin; Glycosaminoglycans; Humans; Hypertension; L-Lactate Dehydrogenase; Macromolecular Substances; Metabolic Diseases; Necrosis; Oxidoreductases; Sclerosis; Thrombosis; Time Factors; Vasa Vasorum

Hepatoportal sclerosis accompanied by dense elastic fibre deposition is generally regarded as the primary lesion in the development of idiopathic portal hypertension (IPH). This study was performed to clarify the mechanism of elastic fibre deposition in the peripheral portal tracts of IPH liver in relation to serum anti-endothelial cell antibodies (AECA). In-vitro experiments were performed using human dermal microvascular endothelial cells (HMVEC) and patients' sera. The presence of serum AECA was assayed by a cell-based enzyme-linked immunosorbent assay (ELISA) using HMVEC. Immunohistochemical analysis of elastin was performed using liver tissue sections of IPH patients. IPH sera contained one or more AECA that could bind to the vascular endothelial cells of the peripheral portal tracts of the liver. When the value of AECA greater than the mean ± 2 standard deviations of healthy controls was regarded as positive, the positive detection rate of either immunoglobulin (Ig)G, IgA or IgM AECA in IPH sera was 30% (10 of 33 cases). IPH sera induced the expression of elastin in HMVEC, which appeared to be associated with the presence of AECA. Apoptosis was also induced in HMVEC by the stimulation with IPH sera. In vivo, elastin expression was observed in the endothelial cells of the peripheral portal tracts of IPH livers in a proportion of cases. The disease pathogenesis of IPH seems to be heterogeneous, and this study elucidated a possible contribution of the induction of elastin expression in the portal vessels to hepatoportal sclerosis of IPH, which might be linked to serum AECA as a causative factor.

Topics: Apoptosis; Autoantibodies; Base Sequence; Case-Control Studies; Cells, Cultured; DNA Primers; Elastin; Endothelial Cells; Humans; Hypertension, Portal; Idiopathic Noncirrhotic Portal Hypertension; Immunohistochemistry; In Vitro Techniques; Liver Cirrhosis; Pancytopenia; Portal Vein; RNA, Messenger; Sclerosis; Splenomegaly

It has been suggested that aortic valve sclerosis (AVS) is an atherosclerotic disease process that can proceed to aortic stenosis. The absence of reports studying an animal model of the early stages of this disease has precluded the development of preventive therapeutic strategies. A cholesterol-fed (0.25% cholesterol in chow) rabbit model of atherosclerosis that is characterized by a moderate level of hypercholesterolemia was studied to determine its efficacy as a model of early AVS. Cellular, structural and morphological changes in the aortic valves of these rabbits were studied.. Twenty rabbits were assigned randomly to four experimental groups: Group 1 received normal chow for 40 weeks; group 2 received 0.25% cholesterol-supplemented chow for 20 weeks; group 3 received 0.25% cholesterol-supplemented chow for 40 weeks; and group 4 received 0.25% cholesterol-supplemented chow for 20 weeks followed by normal chow for an additional 20 weeks. The aortas and aortic valves were analyzed using immunohistochemical and histological methods to detect cellular and structural components of the developing lesions.. All rabbits in groups 2, 3 and 4 developed atherosclerotic lesions in their aortas. Aortic valves from these animals demonstrated thickening, lipid deposition, a change in collagen content and organization, a reorganization of elastin, and the presence of both macrophage infiltrate and osteopontin.. These findings were consistent with the suggestion of a link between atherosclerosis and AVS. Results were also similar to changes reported in human sclerotic aortic valves, suggesting the suitability of this rabbit model of atherosclerosis as a model for AVS.

Topics: Animals; Aorta; Aortic Valve; Arteriosclerosis; Cholesterol, Dietary; Collagen; Diet, Atherogenic; Disease Models, Animal; Elastin; Humans; Hypercholesterolemia; Immunohistochemistry; Lipids; Macrophages; Male; Osteopontin; Phosphoproteins; Rabbits; Random Allocation; Sclerosis; Sialoglycoproteins

To assess further the influence of heparinoids on arterial sclerosis, we compared the effects of standard heparin and of a low-molecular-weight (low-mol-wt) heparin (CY 216) in vitro on proliferation of cultured arterial smooth muscle cells (SMC) from rat aorta and in vivo on the sclerotic response of rat thoracic aorta to injury with a balloon catheter (SMC proliferation and deposition of elastin and collagen in the intima-media, using biochemical and histomorphologic techniques). Both heparinoids decreased replication of SMC in vitro in a similar dose-dependent manner. In vivo, heparin treatment [continuous intravenous (i.v.) administration, 60 IU/h/kg body weight (0.35 mg/h/kg)] inhibited all aspects of the aortic reaction for < or = 28 days after injury: synthesis of DNA (early peak of thymidine incorporation into DNA on D3.5); accumulation of DNA, collagen and elastin on D14 and D28; intimal thickening on D14. An equivalent treatment with CY 216 [60 antiactivated factor X (Xa) IU/h/kg (0.71 mg/h/kg)] exerted similar though less intense effects on the reaction of intima-media, as assessed biochemically, but reduced formation of neointima in a proportion nearly identical to that of heparin. In some respects, which appear to be related mainly to the fibrotic reaction of aortic media to injury, heparin tended to be a slightly more potent antisclerotic agent than CY 216 although, owing to pharmacokinetic differences, CY 216 had stronger plasma anti-Xa activity than heparin.

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Catheterization; Cell Division; Cells, Cultured; Collagen; DNA; Elastin; Heparin; Male; Muscle, Smooth, Vascular; Nadroparin; Rats; Rats, Wistar; Sclerosis; Thrombin