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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the interactions of lipoproteins, connective tissue components and cells, mouse peritoneal macrophages were incubated in the presence of human low density lipoproteins (LDL) that had been complexed with pig aortic proteoglycans (PG) or incubated in the presence of soluble collagen and/or lysyl oxidase, which catalyses the formation of cross-linkages in collagen and elastin by oxidising epsilon-amino groups of lysine residues to aldehydes. Soluble and insoluble PG-LDL complexes increased the incorporation of [3H]oleate into cellular cholesteryl esters (CE) 1.6- and 2.8-fold, respectively, while LDL incubated with collagen and lysyl oxidase had no effect compared to control LDL. As judged on the basis of incubations with fucoidin, spermine and 125I-labelled lipoproteins, the mechanism of internalisation of the PG-LDL complexes is different from that of acetylated LDL or dextran sulphate-LDL complexes. The formation of PG-LDL complexes in the arterial intima may lead to an increased uptake of lipoproteins by intimal macrophages during the early phase of atherogenesis.
Atherosclerosis 1986 Oct
PMID:The effect of proteoglycans, collagen and lysyl oxidase on the metabolism of low density lipoprotein by macrophages. 287 75

Atherosclerosis was induced in growing chickens by the administration of a diet containing elevated levels of cholesterol and vitamin D3. The effect of this diet on the accumulation of insoluble elastin and the synthesis of soluble and insoluble elastin in the thoracic aortas of these animals was measured. Although the diet resulted in significant increases in levels of cholesterol, 25-OH vitamin D3 and calcium in plasma, increased levels of cholesterol and calcium in aortic tissue, and histological evidence of aortic lipid deposition, there were no detectable differences between experimental and control animals in either the rate or the time course of accumulation of total insoluble elastin in the thoracic aorta, or in the rate and time course of synthesis of soluble and insoluble elastin. These data suggest that, at least in this model, any effect of atherosclerosis on aortic elastin production must be either small or so localized as to be not measurable by the methods used.
Atherosclerosis 1985 Mar
PMID:The effect of induced atherosclerosis on the synthesis of elastin in chick aortic tissue. 298 56

All large arteries contain elastin, collagen, and muscle which can be seen with light microscopy and transmission electron microscopy. Elastin forms an internal elastic lamina (IEL) in all arteries, but also forms multiple fenestrated sheets in the media of the aorta and other large arteries. The fenestrations in the media are larger than those in the IEL. The adventitial elastin is more fibrous and often contains tubular elastin surrounding vasa vasorum when prepared by removing all non-elastin by placing the aorta in 0.1 N NaOH at 70-75 degrees C for five hours. The fenestrations are larger near branches and in an experimentally created poststenotic dilatation. Atherosclerosis appears associated with both new elastin formation in early atherosclerosis and elastolysis in late disease.
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PMID:Arterial elastin as seen with scanning electron microscopy: a review. 304 76

Transforming growth factor-beta, a peptide growth factor, is known to be a multifunctional regulator of cellular activity. The effect of this growth factor on extracellular matrix formation is well established, but its effects on elastin, a critical component of lung, skin, and blood vessels are unknown. In the present study, by use of an Enzyme-Linked Immunoassay method, we found that transforming growth factor-beta strongly increased elastin production in cultured porcine aortic smooth muscle cells. In a dosage-dependent study, 1.0-10.0 ng/ml transforming growth factor-beta promoted elastin production 2-3 fold. In a time-dependent study, at least an 8 h pre-treatment with 10.0 ng/ml transforming growth factor-beta was required for sustained increases in elastin production. The effects of transforming growth factor-beta on cultured aortic smooth muscle cells suggest that this cytokine may be an important mediator of elastin formation during atherosclerosis and hypertension.
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PMID:The elastogenic effect of recombinant transforming growth factor-beta on porcine aortic smooth muscle cells. 316 37

Elastin is a major component of the artery wall and, because of their involvement in atherosclerosis, the interaction of lipoproteins with elastin may be of considerable importance. Previous studies of the interactions between elastin and lipoproteins have been carried out in idealised systems which do not retain the structure of the elastin. In this study we have measured the uptake of both low density lipoprotein (LDL) and high density lipoprotein (HDL) by arterial preparations and have tried to assess the importance of the different steps of preparation on the results. By comparing elastin from different sources and different degrees of extraction and delipidation we have tried to make some inferences about the nature of the interaction between elastin and lipoproteins in the hope that we can better understand the importance of this interaction in vivo.
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PMID:Some factors influencing the interactions of plasma lipoproteins with arterial elastin. 317 4

Copper deficiency has been shown to result in severe cardiovascular lesions in several species of animals. The principal carbohydrate in the copper-deficient diet most often used with rats is sucrose, which is known to have adverse effects on carbohydrate and lipid metabolism and thus may contribute to cardiovascular disorders. These observations prompted experiments in which starch and fructose were substituted for sucrose in a copper-deficient diet, to see if the effects of the copper deficiency might be modified. In the hearts from rats fed copper-deficient diets with fructose or sucrose, there was marked, mostly ventricular hypertrophy, and mild to severe myocardial inflammation, degeneration, and fibrosis. Aneurysm of the left ventricle and pericarditis also were common. Hearts from the starch, copper-deficient groups were much less hypertrophic, and very few were affected by myocardial inflammation, degeneration, or fibrosis. Defects of elastin or other structures were not observed in the aortas or pulmonary or coronary arteries of any specimens.
Atherosclerosis 1988 Dec
PMID:Dietary fructose exacerbates the cardiac abnormalities of copper deficiency in rats. 324 Mar 32

Current concepts of the pathogenesis of atherosclerosis have been reviewed, emphasizing some of the similarities of the mechanisms and events involved to those in inflammation. Figure 2 is a schematic summary of these events. Hyperlipidemia, or some component of hyperlipidemic serum, as well as other risk factors, are thought to cause endothelial injury, resulting in adhesion of platelets and/or monocytes and release of PDGF (and other growth factors), which leads to smooth muscle migration and proliferation. It is clear that endothelial injury need not be denuding, and in fact may consist of altered endothelial function (dysfunction); adhesion of monocytes, increased permeability of endothelium, and disturbances in growth control can occur without morphologically obvious endothelial injury. Hyperlipidemia, hypertension, smoking, immune injury, and other risk factors may contribute to this endothelial dysfunction in different ways and sometimes in combination. Smooth muscle cells produce large amounts of collagen, elastin, and proteoglycans and these form part of the atheromatous plaque. Hyperlipidemia contributes in a number of ways (as discussed earlier), and indeed, in the severely hypercholesterolemic patient, such as one with familial hypercholesterolemia, is alone sufficient to cause atherosclerosis in the absence of other risk factors. Foam cells of atheromatous plaques are derived both from macrophages and from smooth muscle cells; from macrophages via the beta-VLDL receptor and also possibly by way of LDL modification, recognized by the acetyl-LDL receptor (such as oxidized LDL); and from smooth muscle cells by less certain mechanisms. Extracellular lipid is derived from insudation from the lumen, particularly in the presence of hypercholesterolemia, and also from degenerating foam cells. Cholesterol accumulation in the plaque should be viewed as reflecting imbalance between influx and efflux, and it is possible that high-density lipoprotein is the molecule which helps clear the cholesterol from these accumulations (134). The diagram (right) also depicts the possibility that smooth muscle proliferation may occur without endothelial injury at all. There are several postulated mechanisms for such an occurrence: loss of growth control, direct smooth muscle injury (such as by LDL), and autonomous proliferation by the mechanisms suggested by Benditt. The theoretical scheme presented is based largely on in vitro work, only partly substantiated by experimental and human studies, and does not explain the precise mechanisms by which all risk factors increase the susceptibility to atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The pathogenesis of atherosclerosis: atherogenesis and inflammation. 327 59

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.
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PMID:Aging of the extracellular matrix and its pathology. 328 58

Migration of smooth muscle cells (SMCs) of the media through the internal elastic lamina to the intima in response to various chemoattractants is considered to be an important event in the development of atherosclerosis. We evaluated the influence of elastin peptides prepared from normal aorta on migration of cultured rat aortic SMCs in vitro. Studies with filters coated with elastin peptides in a modified Boyden's chamber showed that the migratory response of cultured rat aortic SMCs in response to platelet-derived factors was impeded by filter-bound elastin peptides. The inhibitory effect appeared to be relatively specific for elastin peptides and for SMCs, as other matrix components (Types I, III, IV, and V collagens and fibronectin) did not impede SMC migration, and polymorphonuclear leukocytes were not impeded by elastin peptides. Elastin peptides in solution in the lower well caused the migratory response, and this response was also inhibited by filter-bound elastin peptides. Attractants such as platelet-derived factors and elastin peptides are likely to be present in the matrix around migrating SMCs. These studies suggest that elastin peptides adhering to the substratum or elastin, a major component of elastic fiber, may be one of the natural inhibitors of vascular SMC migration in response to chemoattractants in the fluid phase.
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PMID:Substratum-bound elastin peptide inhibits aortic smooth muscle cell migration in vitro. 331 79

As a result of aging, a variety of structural and biochemical changes occur in arterial walls that result in hemodynamic adaptations. With age, there is a thickening of intima and media, together with an increase in the number of smooth muscle cells, synthesis of collagen and elastin, and deposition of calcium, glycosaminoglycans, free and esterified cholesterol, and sphingolipids. These changes are similar to those observed in atherosclerosis, which is accompanied by marked increases of intimal smooth muscle cells and connective tissue constituents. The net effects of both aging and atherosclerosis are a loss of elasticity and distensibility. This results in a decrease in arterial compliance or capacitance, which in turn means that with increasing age systolic blood pressure (SBP) tends to be higher, and diastolic blood pressure (DBP) lower. As a consequence of structural changes both in myocardium and vessels, cardiac output and renal and hepatic blood flow undergo adaptive alterations in order to meet the requirements of central hemodynamics and peripheral circulation. The implications of these processes of aging demand appropriate treatment of cardiovascular disorders, in particular hypertension, which occurs in 30-50% of patients above the age of 60 years. Appropriate treatment may demand dose adjustment and careful selection of antihypertensive drugs with a minimum of side effects, which additionally are capable of diminishing preload and afterload.
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PMID:Aging and the cardiovascular system. 344 May 23


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