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

This review summarizes progress in nonenzymatic glycosylation research of potential relevance to atherosclerosis using a hypothetical model based on current concepts of atherogenesis. Recently, new information has been presented showing that the initial Amadori product undergoes a series of further reactions and rearrangements to form adducts, called advanced glycosylation end products (AGE). These products are irreversible and accumulate indefinitely on long-lived molecules. These AGE covalently trap soluble plasma proteins, act as signals for macrophage recognition and uptake, and induce mutations in double-stranded plasmid DNA. Covalent trapping of low-density lipoprotein (LDL) by AGE on collagen or elastin could promote lipid accumulation in the arterial wall, whereas AGE trapping of von Willebrand factor would increase platelet adhesion and aggregation leading to intimal smooth muscle cell proliferation. Recognition and uptake of AGE-proteins by scavenging macrophages could further contribute to the process of atherogenesis by stimulating release of macrophage secretory products such as macrophage-derived growth factor. Accumulation of AGE on smooth muscle cell DNA might also enhance arterial smooth muscle cell proliferation by increasing the rate of mutations affecting growth controls. This model should provide the basis for future experiments.
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PMID:Role of nonenzymatic glycosylation in atherogenesis. 351 22

A role of von Willebrand factor-mediated platelet function in porcine atherogenesis is strongly suggested by these studies. This influence of platelet function is probably most important in experimental systems that involve long-term observation and low or moderately elevated levels of serum cholesterol. On the other hand, effects of platelet function on development of atherosclerosis in animals with extremely high serum cholesterol levels are difficult to demonstrate and may be of relatively less importance. These observations are consistent with the results of numbers of recent studies describing the relationship of vascular injury to intimal smooth muscle cell proliferation. There is considerable evidence that lipid-rich intimal lesions occur in hypercholesterolemic animals with no antecedent denudation of endothelium or platelet adherence. It is difficult to ascribe intimal proliferation to platelet effects in this setting. On the other hand, endothelial cells, smooth muscle cells, and monocytes, which are all known to be involved in the atherosclerotic process, can produce mitogenic and chemotactic proteins, including platelet-derived growth factor. Therefore, metabolic aberrations of various kinds, including those initiated by mechanical injury or hypercholesterolemia, may promote proliferation in the vascular wall and resultant lesion development. Data from studies of pigs with vWD suggest a contribution of platelets to this process, but the effects of this contribution are modulated by numbers of variables, most of which are yet to be identified. The control of these multiple variables will be necessary before a clear understanding of the magnitude of the platelet-mediated effects can be gained. This will require carefully defined conditions of hypercholesterolemia, special attention to the immunologic variables and study of properly selected vascular segments under known conditions of flow. This later element will be especially important in the study of vWF-mediated platelet function, since shear forces are a critical determinant of vWF function. Systems that model flow conditions in various segments of the aorta, carotid, and coronary arteries are presently under development for this purpose. Finally, studies examining the molecular basis of vWF-mediated and other platelet functions will probably guide the most productive use of these models. Platelet membrane glycoprotein (GP) receptor Ib and the complex GP IIb and IIIa have been shown in ex vivo studies to be binding sites for vWF molecules.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Porcine von Willebrand disease: implications for the pathophysiology of atherosclerosis and thrombosis. 355 Aug 94

There is abundant evidence that changes in diet and various types of vessel wall injury can independently induce the growth of arterial lesions in experimental animals. These lesions closely resemble those found in humans with atherosclerosis. Whether endothelial injury or accumulation of lipoprotein in the arterial intima is the initial event, the progression of the disease is characterized by changes in the neointima that favor the deposition of lipid. The metabolism of proteoglycans may be especially important in this process; this is relevant to diabetes because changes in proteoglycan metabolism are associated with this disease. Insulin and growth hormone may favor the proliferation of smooth muscle cells in the arteries of diabetic patients. Many agents, which are potentially injurious to the endothelium, accentuate the response of the vessel wall to injury. Modifications of the thrombotic process, such as increased production of thromboxane by platelets, decreased production of prostacyclin by the endothelium, and increased production of von Willebrand factor further enhance the thrombotic process and may be important in the initiation and subsequent progression of atherosclerosis in diabetics. Alterations in lipoprotein metabolism may also facilitate the development of endothelial injury.
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PMID:Pathogenesis of atherosclerosis. 390 56

This review summarizes the progress of research in nonenzymatic glycosylation that is of potential relevance to atherosclerosis and relates this knowledge to the accelerated large-vessel disease observed in diabetics through a hypothetical model based on current concepts of atherogenesis. Critical new information has recently been obtained about complex glycosylation adducts, which form very slowly through a series of further reactions and rearrangements from the initial Amadori product. These adducts, called advanced glycosylation end products (AGE), are not reversible like the Amadori product. Thus, they continue to accumulate indefinitely on long-lived molecules such as collagen and nucleic acids. AGE covalently trap soluble plasma proteins, act as signals for macrophage recognition and uptake, and induce mutations in double-stranded plasmid DNA. Covalent trapping of low-density lipoproteins by AGE on collagen may promote excessive lipid accumulation in the arterial walls of diabetics, whereas trapping of von Willebrand factor by AGE may increase platelet adhesion and aggregation, leading to smooth muscle cell proliferation in the arterial intima. Recognition and uptake of AGE-protein derivatives by scavenging macrophages may further contribute to the process of atherogenesis by stimulating the release of such macrophage secretory products as macrophage-derived growth factor. Accumulation of AGE on smooth muscle cell DNA may also enhance proliferation of arterial smooth muscle cells by increasing the rate of mutations that affect growth control.
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PMID:Protein glycosylation and the pathogenesis of atherosclerosis. 390 59

Coagulation factor VIII, von Willebrand factor, antithrombin, fibrinogen, plasminogen activator capacity, and inhibitors of fibrinolysis, including a recently discovered fast inhibitor of tissue plasminogen activator, were measured three to six months after myocardial infarction in 116 male and 32 female patients aged less than 45 and in 136 age and sex matched random controls. Plasma concentrations of fibrinogen and the fast inhibitor of tissue plasminogen activator were raised in male patients (with or without correction for orosomucoid levels, blood group distribution, tobacco and alcohol consumption, and weight/height index) and plasminogen activator capacity was reduced. In female patients the concentrations of factor VIII, von Willebrand factor, the fast inhibitor of tissue plasminogen activator, alpha 2-antiplasmin, and C1 inhibitor were significantly increased. The increase in factor VIII concentrations depended strongly on a persisting inflammatory response. Multivariate analysis indicated that a combination of fibrinogen and tissue plasminogen activator inhibitor concentrations gave the best independent discrimination between male patients and controls. For female patients the best combination was von Willebrand factor and tissue plasminogen activator inhibitor. Male patients with multiple vessel atheromatosis at coronary angiography had higher fibrinogen concentrations than those with atheromatosis of a single vessel. Atheromatosis was defined as sharp-edged, plaque-like, or irregular indentations, often multiple, into the vessel lumen without features suggesting fibromuscular hyperplasia.
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PMID:Haemostatic function in myocardial infarction. 394 83

New concepts about the pathogenesis of atherosclerosis in diabetes mellitus are presented. Emphasis is given to alterations of endothelial function, as indicated by von Willebrand factor activity, prostacyclin release, and fibrinolytic activity in diabetes mellitus. Previous work on platelet aggregation and arachidonic acid metabolism is updated and recent findings are emphasized. The atherogenic mix of elevated low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol levels in uncontrolled diabetes mellitus is noted. The lipid hypothesis is extended by consideration of very low-density lipoprotein and intermediate-density lipoprotein metabolism in diabetes. Lipoprotein-cell interactions that may contribute to atherosclerosis are reviewed and suggestions are made for future research in order to clarify the pathogenesis of atherosclerosis in diabetes mellitus.
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PMID:New concepts about the pathogenesis of atherosclerosis in diabetes mellitus. 642 41

Primary cultures of confluent human endothelial cells (ECM) were grown in media containing the major lipoproteins (LP) and lipoprotein deficient serum (LDS). The release of 6-keto-PGF1 alpha, von Willebrand factor (VIII RAg) and apolipoproteins (apo) A-I and A-II were investigated by radioimmunoassay. The cell-associated VIII RAg, apo A-I and apo A-II were also confirmed by fluorescein antibodies, and the synthesis of the apolipoproteins was examined by incorporation of [3H]leucine. Apo A-I and apo A-II were located and synthesized in ECM, yet only apo A-I was released into the medium. Very low density (VLDL) and low density lipoproteins (LDL) in concentrations of 50-600 micrograms/ml stimulated release of apo A-I. Stimulation of ECM for 5 min with thrombin (T) or arachidonic acid (A) did not induce apo A-I release. VIII RAg was always released into the media from ECM. The release was not affected by the lipoproteins. VIII RAg was also localized on the cell surface (VIII RAgC) and approximately 80% was released by trypsin. LDL stimulated the occurrence of factor VIII RAg on the cell surface. 6-Keto PGF1 alpha was always released into the medium and the production was stimulated by T and AA. The main lipoproteins (50-600 micrograms/ml) and apo A-I and A-II did not affect the release of 6-keto-PGF1 alpha. This study shows that endothelial cells synthesize and release proteins important for thrombogenesis and atherosclerosis. The release of apolipoproteins A-I was stimulated by VLDL and LDL, and the concentration of cell-related factor VIII RAg was stimulated by LDL.
Atherosclerosis 1984 Mar
PMID:The effect of lipoproteins on the synthesis of prostacyclin, von Willebrand factor and apolipoproteins A-I and A-II in cultured human endothelial cells. 642 92

The prevalence of von Willebrand's disease (VWD) in Western European countries and Israel was assessed. Possible patients were identified initially by questionnaire and those with plasma levels of von Willebrand factor antigen ( WFAg ; factor VIII related antigen) less than 1 u/dl (less than 1%) were confirmed by immunoradiometric assay performed at four reference centres. The prevalences of severe VWD in Scandinavian countries were similar to each other and about 10 times greater than those in other Western European countries. The prevalence in Israel was intermediate. The Registry will form the basis for future non- invasive epidemiological studies of atherosclerosis in these individuals.
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PMID:Atherosclerosis and von Willebrand factor. I. Prevalence of severe von Willebrand's disease in western Europe and Israel. 660 12

The development of coronary and aortic atherosclerosis was determined after balloon catheter injury of coronary arteries and administration of an atherogenic diet in normal pigs and pigs that were homozygous and heterozygous for von Willebrand's disease. Coronary atherosclerosis developed to a similar degree in all three phenotypic groups. The mean intimal thickness at the site of maximal thickness in ballooned vessels was .51 mm in the normal pigs, .67 mm in carrier pigs, and .55 mm in bleeder pigs. The intimal thickness of non-ballooned vessels was .28 mm in normal pigs, .28 mm in carrier pigs, and .35 mm in bleeder pigs. Fibrous lesions of atherosclerosis covered an average of 3.88% of the aorta in normal pigs, 2.83% in carrier pigs, and 2.37% in bleeder pigs. The difference between the aortic lesions of normal animals and bleeders was significant (P less than .05). Absence of von Willebrand factor was associated with limited resistance to atherosclerosis in the aortas of experimental pigs but did not affect the development of atherosclerosis in either ballooned or nonballooned coronary arteries. These findings suggest, first, that von Willebrand factor function is not essential to the development of the atherosclerotic lesion in this model and, second, that the role of the von Willebrand factor in the development of atherosclerosis is complicated and appears to involve interaction with variables not yet defined.
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PMID:Susceptibility to atherosclerosis in aortas and coronary arteries of swine with von Willebrand's disease. 697 May 27

The extent of coronary and aortic atherosclerosis was examined in pigs following balloon-catheter injury of coronary arteries and subsequent feeding of an atherogenic diet for 4 months. The pigs were either exposed intermittently to 100 ppm carbon monoxide or to ambient air alone. Three types of pigs were used: normals, homozygotes for von Willebrand's disease (bleeders), and heterozygotes (carriers). The 3 types of pigs developed coronary artery intimal lesions of similar thickness. Aortic lesions, quantified as percent of aortic surface involved with sudanophilia and raised fibrous plaques, were slightly less extensive in bleeder pigs than in normals. Carbon monoxide exposure did not increase the thickness of coronary artery intimal lesions, nor did it increase the percent of aortic surface involved with sudanophilia or raised fibrous lesions. These results suggest that exposure to low levels of carbon monoxide does not perceptibly enhance atherogenesis induced by hypercholesterolemia. None of 14 bleeder pigs showed evidence of myocardial infarction, despite significant coronary artery narrowing. Of the 24 normal and carrier pigs, 5 showed myocardial infarction. Four of these 5 pigs were exposed to carbon monoxide, while 1 was not exposed. These findings suggest that exposure to low levels of carbon monoxide may increase the incidence of myocardial infarction and that the absence of von Willebrand factor may be protective.
Atherosclerosis 1982 Jun
PMID:Effect of carbon monoxide on atherogenesis in normal pigs and pigs with von Willebrand's disease. 698 17


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