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

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

The presence of specific receptors for the metabolism of acetylated low density lipoprotein (AcLDL) and beta-migrating very low density lipoprotein (beta-VLDL) was demonstrated in thioglycolate-elicited peritoneal macrophages from both atherosclerosis-susceptible White Carneau (WC) and resistant Show Racer (SR) pigeons. Macrophages from both breeds metabolized AcLDL through a single class of receptors that were similar, but not identical, to the scavenger receptors described in mammalian macrophages. Both pigeon and mammalian AcLDL bound to this receptor. At 37 degrees C, AcLDL was internalized and degraded in the lysosomes, and cholesterol esterification and cholesteryl ester accumulation were stimulated. As in mammalian macrophages, AcLDL receptor activity was not down-regulated by cholesterol loading. In contrast, AcLDL binding was poorly competed for by fucoidin or polyinosinic acid, and the magnitude of cholesteryl ester accumulation was only about one-half of that seen with mouse peritoneal macrophages. Pigeon beta-VLDL bound to both a high and a low affinity site on pigeon macrophages. Binding to the high affinity site was calcium-dependent, pronase-sensitive, and down-regulated by cholesterol loading. Cholesterol esterification and cholesteryl ester accumulation with beta-VLDL were stimulated to an equal or greater extent than with AcLDL. Unlike mammalian macrophages, the pigeon beta-VLDL receptor did not require apolipoprotein E, as evidenced by the lack of apoE in pigeon lipoproteins and by the failure of rabbit beta-VLDL, containing apoE, to compete for binding. Pigeon LDL, but not mammalian LDL, was recognized by the pigeon beta-VLDL receptor, suggesting that like the mammalian beta-VLDL receptor, the pigeon beta-VLDL receptor may be a form of an LDL receptor. This was an unexpected finding since pigeon fibroblasts and smooth muscle cells in culture do not express LDL receptors. Thus, pigeon macrophages have receptors for the uptake of abnormal lipoproteins that could play a role in the development of macrophage-derived foam cells that are prevalent in the early stages of atherosclerosis in this species. No quantitative or qualitative differences in these receptors, however, were identified that could account for the differences in atherosclerosis susceptibility between the WC and SR breeds.
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PMID:Lipoprotein metabolism by macrophages from atherosclerosis-susceptible White Carneau and resistant Show Racer pigeons. 341 Dec 39

Oral administration of thermally oxidized soya bean oil (TO) increased the level of lipid peroxides in human plasma, mainly in chylomicrons. No changes were observed after fresh oil (FO) intake. Human chylomicrons obtained after TO ingestion were rich in lipid peroxides and degraded more rapidly by cultured mouse macrophages than chylomicrons after FO. The uptake of TO chylomicrons by macrophages occurred via a saturable process and was partially inhibited by beta-very low density lipoprotein as well as by acetyl-low density lipoprotein and fucoidin. A 48-h incubation of macrophages with TO chylomicrons caused a 10-fold higher accumulation of cholesterol ester mass in the cells than the incubation with FO chylomicrons. These studies suggest that chylomicrons containing lipid peroxides may be taken up by mouse macrophages by mediation of beta-VLDL receptor as well as by acetyl-LDL receptor, and show a potential pathway by which chylomicrons obtained after ingestion of heated oil could contribute to accumulation of cholesterol esters in macrophages.
Atherosclerosis 1987 Jul
PMID:The effect of thermally oxidized soya bean oil on metabolism of chylomicrons. Increased uptake and degradation of oxidized chylomicrons in cultured mouse macrophages. 363 53

Large VLDL from subjects with HTG but not normal humans bind with high affinity to both the classic LDL receptor present on all cells and the beta-VLDL receptor of macrophages. Binding of HTG-VLDL to the LDL receptor is mediated by a thrombin-accessible conformation of Apo E that is absent in normal VLDL. Binding of HTG VLDL to the beta-VLDL receptor appears to be mediated by one or more apo B species. We find that thrombin-accessible apo E is required for uptake of HTG-VLDL via the LDL receptor but not by the beta-VLDL receptor. Domains within apo B that are present in native chylomicrons and HTG-VLDL or created in vitro with thrombin appear to be required for binding to the beta-VLDL receptor but not the LDL receptor. Triglyceride-rich lipoproteins could be processed in vivo by thrombin or other proteases for preferential uptake and disposal by the beta-VLDL receptor pathway. This process may be involved in the foam cell accumulation and atherosclerosis associated with some types of hypertriglyceridemia.
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PMID:Interactions of triglyceride-rich lipoproteins with receptors: modulation by thrombin. 378 67

The recently cloned very low density lipoprotein (VLDL) receptor binds triglyceride-rich, apolipoprotein-E-containing lipoproteins with high affinity. The observation that VLDL receptor mRNA is abundantly expressed in extracts of tissues such as skeletal muscle and heart, but not liver, has led to the hypothesis that this receptor may facilitate the peripheral uptake of triglyceride-rich lipoproteins. However, little information is available concerning the types of cells that express this receptor in vivo. As expression of the VLDL receptor in the vascular wall might have important implications for the uptake and transport of triglyceride-rich lipoproteins, and perhaps facilitate the development of atherosclerosis in hypertriglyceridemic individuals, we used in situ hybridization and immunohistochemistry to determine whether VLDL receptor mRNA and protein was expressed in human vascular tissue. We observed expression of the receptor by both endothelial and smooth muscle cells within normal arteries and veins, as well as within atherosclerotic plaques. In the latter, the VLDL receptor was also expressed by macrophage-derived foam cells. The widespread distribution of the VLDL receptor in vascular tissue suggests a potentially important role for this receptor in normal and pathophysiological vascular processes.
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PMID:Expression of very low density lipoprotein receptor in the vascular wall. Analysis of human tissues by in situ hybridization and immunohistochemistry. 866 83

To elucidate the regulation of very low density lipoprotein (VLDL) receptor gene expression, we administered to rabbits for 14 days gemfibrozil, a fabric acid derivative and a lipid lowering drug that is also included among peroxisome proliferators. VLDL receptor mRNA levels were examined by Northern blot analysis. The VLDL receptor mRNA levels in retroperitoneal adipose tissue and in gastrocnemius muscle were increased 6.9-fold and 3.7-fold, respectively, with gemfibrozil treatment, but no marked changes were observed in the heart, the organ in which VLDL receptor is most highly expressed. In the liver, VLDL receptor mRNA was not detected either before or after gemfibrozil administration. Lipoprotein lipase (LPL) and long-chain acyl coenzyme A synthetase (ACS) mRNA levels were also increased in parallel in adipose tissue. The enhanced expression of VLDL receptor mRNA may contribute to the increase of triglyceride-rich lipoprotein catabolism in peripheral tissues such as adipose tissue and muscles.
Atherosclerosis 1996 Oct 25
PMID:Effects of gemfibrozil administration on very low density lipoprotein receptor mRNA levels in rabbits. 890 47

The expression of very low density lipoprotein (VLDL) receptor mRNA in atherosclerotic lesions in rabbits was investigated. To examine the expression of the VLDL receptor in the vascular wall, poly(A)+ RNA was isolated from whole aortas of cholesterol-fed New Zealand White (NZW), Watanabe heritable hyperlipidemic (WHHL), and normal NZW rabbits, and then Northern blot analysis was performed. The VLDL receptor mRNA was detected in aortas from both NZW rabbits fed 0.5% cholesterol for 16 weeks and 12-month-old WHHL rabbits, whereas no expression was seen in normal NZW rabbit aortas. To further determine the localization of the VLDL receptor mRNA, in situ hybridization using digoxigenin-labeled riboprobes and immunohistochemistry using monoclonal antibodies against each cell component were performed. Early atherosclerotic lesions, termed fatty streaks, in the NZW rabbits fed 0.5% cholesterol for 4 weeks demonstrated strong expression of the VLDL receptor mRNA by macrophages. The VLDL receptor mRNA was also expressed in more advanced atherosclerotic lesions from both atherogenic animal models. The predominant origin of the VLDL receptor mRNA-positive cells was macrophages, and some intimal smooth muscle cells appeared to express a weak but significant signal in these advanced lesions. Our findings suggest that the VLDL receptor expression may play a role in the development of atherosclerosis.
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PMID:Expression of very low density lipoprotein receptor mRNA in rabbit atherosclerotic lesions. 895 20

The VLDL receptor is made up of five functional domains that resemble the LDL receptor. In mammals, the receptor is highly expressed in muscle and fat cells, while in chicken, it is abundant in oocytes. The extremely high degree of amino acid conservation of the VLDL receptor during the evolution suggests that the receptor plays an essential role in vertebrates. Recent studies on the chicken VLDL receptor revealed that the receptor plays a key role in the uptake of yolk precursors in oocytes and mediates the growth of oocytes. The VLDL receptor is an essential receptor in avian species and the receptor-deficient mutant hens are sterile and exhibit severe hyperlipidemia with aortic atherosclerosis.
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PMID:VLDL receptor in health and disease: interview with a receptor in avian oocytes and mammalian muscle and fat cells. 922 12

Expression of VLDL receptor mRNA during differentiation of HL-60 cells was investigated by Northern analysis. The expression induced in 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3)-treated cells was 3 times that in untreated cells, while LDL receptor mRNA expression was unchanged. VLDL receptor mRNA levels were not changed in macrophages caused to differentiate from HL-60 cells by treatment with phorbol 12-myristate 13-acetate (PMA). Treatment of sarcoma cells which possess the vitamin D receptor (MG-63 cell line) with 1 alpha,25(OH)2D3 did not affect VLDL receptor mRNA levels. Therefore, 1 alpha,25(OH)2D3 induces VLDL receptor mRNA in HL-60 cells through differentiation-dependent mechanisms.
Atherosclerosis 1997 Aug
PMID:1 alpha,25-dihydroxyvitamin D3 induces very low density lipoprotein receptor mRNA expression in HL-60 cells in association with monocytic differentiation. 925 6

To elucidate the mechanism of triglyceride (TG) accumulation in adipocytes induced by TG-rich lipoproteins, we examined the effect of beta-very low density lipoprotein (beta-VLDL) on TG accumulation in 3T3-L1 adipocytes. Beta-VLDL did not induce TG accumulation in 3T3-L1 preadipocytes but in 3T3-L1 adipocytes. TG accumulation was significantly inhibited by cytochalasin B, an inhibitor of receptor mediated endocytosis. In contrast, cytochalasin B did not inhibit free fatty acid induced TG accumulation in adipocytes. The binding of [125I]beta-VLDL to preadipocytes was inhibited completely by both beta-VLDL and LDL. In sharp contrast, the binding of [125I]beta-VLDL to adipocytes was inhibited completely by beta-VLDL, but partially by LDL. The VLDL receptor mRNA was only expressed in adipocytes. These results suggest that beta-VLDL induced TG accumulation in adipocytes may be mediated through the VLDL receptor pathway.
Atherosclerosis 1997 Nov
PMID:Beta-very low density lipoprotein induces triglyceride accumulation through receptor mediated endocytotic pathway in 3T3-L1 adipocytes. 939 73


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