Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low HDL-cholesterol (HDL-C) levels may elevate atherosclerosis risk, and often associate with hypertriglyceridemia (HTG); however, the metabolic causes of low HDL-C levels with or without HTG are poorly understood. We studied the turnover of radioiodinated HDL apolipoproteins, apo A-I and apo A-II, in 15 human subjects with low HDL-C, six with normal plasma TG levels (group 1) and nine with high TG (group 2), and compared them to 13 control subjects with normal HDL-C and TG levels (group 3). The fractional catabolic rate (FCR) was equally elevated in groups 1 and 2 vs. group 3 for both apo A-I (0.313 +/- 0.052 and 0.323 +/- 0.063 vs. 0.245 +/- 0.043 pools/d, P = 0.003) and apo A-II (0.213 +/- 0.036 and 0.239 +/- 0.037 vs. 0.185 +/- 0.031 pools/d, P = 0.006). Thus, high FCR characterized low HDL-C regardless of the presence or absence of HTG. In contrast, transport rate (TR) of apo A-I did not differ significantly among the groups and the apo A-II TR differed only between groups 2 and 3 (2.15 +/- 0.57, 2.50 +/- 0.39, and 1.83 +/- 0.48 mg/kg per d for groups 1 to 3, respectively, P = 0.016). Several HDL-related factors were similar in groups 1 and 2 but differed in group 3, as with FCR, including the ratio of lipoprotein lipase to hepatic lipase activity (LPL/HL) in post-heparin plasma, the ratio of the HDL-C to apo A-I plus apo A-II levels, and the percent of tracer in the d greater than 1.21 fraction. In linear regression analysis HDL-C levels correlated inversely with the FCR of apo A-I and apo A-II (r = -0.74, P less than 0.0001 for both). Major correlates of FCR were HDL-C/apo A-I + apo A-II, LPL/HL, and plasma TG levels. We hypothesize that lipase activity and plasma TG affect HDL composition which modulates FCR, which in turn regulates HDL-C. Thus, HTG is only one of several factors which may contribute to elevated FCR and low HDL-C. Given the relationship of altered HDL composition with high FCR and low HDL-C levels, factors affecting HDL composition may increase atherosclerosis susceptibility.
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PMID:Increased apo A-I and apo A-II fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridemia. 189 29

Lipoprotein lipase is the rate determining enzyme for the removal of triglyceride rich lipoproteins from the blood stream. We examined whether genetic variation at the lipoprotein lipase gene locus is related to the occurrence of premature coronary artery disease. Two restriction fragment length polymorphisms, revealed by the enzymes HindIII and PvuII, demonstrated alleles designated H1 (17.5 kb), H2 (8.7 kb), P1 (7.0 kb), P2 (4.4 kb and 2.5 kb) respectively. These were studied in 70 Caucasian subjects with severe coronary atherosclerosis in comparison with 122 Caucasian healthy controls. The allelic frequencies for cases and controls were respectively: H2 0.770, 0.579 (P less than 0.001); P2 0.575, 0.554 (P NS). The allelic frequencies of the HindIII and BglII polymorphic sites at the hepatic lipase gene locus were also studied in the same groups of subjects. These showed no differences between cases and controls. We conclude that DNA variation at or adjacent to the lipoprotein lipase gene may contain genetic determinants for the occurrence of premature coronary artery disease.
Atherosclerosis 1990 Nov
PMID:Lipoprotein and hepatic lipase gene variants in coronary atherosclerosis. 198 Aug 16

Accelerated atherosclerosis is a serious complication of chronic renal failure (CRF) treated by peritoneal dialysis. In order to study the pathological mechanisms underlying its development we are using an animal model, namely the C57BL/6J mouse, which develops foam cell-type atherosclerotic lesions after surgical induction of CRF. During atherogenesis, monocyte/macrophages move from the circulation to the blood vessel wall, migrate through the endothelium, imbibe lipid and transform into foam cells. Migration through the endothelium involves proteolysis by plasminogen activator (PA) and uptake of lipids involves hydrolysis of lipoproteins by lipoprotein lipase (LPL). Both of these enzymes are secreted by macrophages. In this paper we report the results of studies on the effect of uremia on the secretion of PA and LPL by macrophages from C57BL/6J mice. The secretion of PA and LPL by macrophages from uremic mice (as defined by BUN levels) was higher than that by cells from control animals. Furthermore, whereas macrophage secretion of PA and LPL was significantly less in normal mice fed a high fat diet than in mice fed rodent chow, it was increased above control levels in uremic animals fed the atherogenic diet. We conclude that increased secretion of PA and LPL by macrophages may contribute to atherogenesis in uremic C57BL/6J mice.
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PMID:Macrophage secretory activity and atherosclerosis during chronic renal failure. 198 12

Dysbetalipoproteinaemia is a genetic disorder characterized by accumulation of lipoprotein remnant particles in the plasma, accelerated atherosclerosis, and the abnormal apoprotein E2. Uncontrolled diabetes mellitus can aggravate the hyperlipidaemia associated with this disorder, presumably by increasing triglyceride synthesis and reducing very low density lipoprotein catabolism by lipoprotein lipase. This report documents the gradual amelioration of dysbetalipoproteinaemia in uncontrolled diabetes mellitus following therapy with exogenous insulin alone. Although the beneficial effects of insulin therapy in this patient may include inhibition of triglyceride synthesis and improved triglyceride catabolism, we propose that insulin may also stimulate clearance of atherogenic remnant lipoprotein particles.
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PMID:Potential role of insulin in the clearance of remnant lipoproteins in dysbetalipoproteinaemia. 199 70

Current knowledge of the links between the sympathetic nervous system and vascular damage in hypertension and atherosclerosis is summarized. The main mechanisms leading to the structural changes of the arterial wall as a consequence of enhanced adrenergic drive are reported. Hemodynamic mechanisms, including increase in pressure leading to changes in the arterioles and alteration of flow pattern with impact mainly in the large arteries, respectively, account for the typical target organ damage observed in hypertension and is involved in the development of atherosclerotic lesions. Regarding the direct effect of catecholamines, the atherogenic effects of epinephrine and norepinephrine in the absence of changes in blood pressure and cholesterol levels have been demonstrated in vivo in monkeys and rabbits. In rats, catecholamine administration induces polyploidization of aortic smooth muscle cells in vivo and in vitro. Regarding the effects of lipid metabolism, adrenergic stimulation may induce free fatty acid transformation into triglycerides with secondary increase in very low density lipoprotein plasma levels and decrease of very low density lipoprotein transformation into high density lipoprotein through circulating lipoprotein lipase inhibition. Catecholamines may also increase cholesterol levels of the arterial wall, probably by triggering the acyl-cholesterol-acyl-transferase activity. Finally, indirect evidence of the pathogenetic role played by the sympathetic system in the development of vascular disease derives from the results of experiments showing that sympatholytic agents are capable of reducing both medial hypertrophy and atherogenesis. beta-Blockers, alpha- and beta-blockers, and centrally acting sympatholytic agents not only ameliorate hemodynamics but also appear to inhibit the direct effects of catecholamines on the arterial wall.
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PMID:Sympathetic drive and vascular damage in hypertension and atherosclerosis. 201 98

Rats administered estrogen-progestin formulation (0.667 mg of synthetic progestin and 0.067 mg of synthetic estrogen/kg body wt) showed increased hepatic cholesterogenesis, as evidenced by an increased activity of HMG-CoA reductase and increased incorporation of labelled acetate into liver cholesterol. Hepatic degradation of cholesterol to bile acids, however, was decreased. There was increased release of lipoproteins into the circulation but their clearance from the circulation was lower as revealed by a decreased activity of lipoprotein lipase of the extrahepatic tissues. Activity of plasma LCAT, which is involved in the transport of cholesterol from the tissues, was also decreased. The increase in serum and aortic cholesterol levels, increase in LDL cholesterol and decrease in HDL cholesterol in rats administered estrogen-progestin formulation suggest that prolonged administration of this formulation may predispose towards atherosclerosis.
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PMID:Mechanism of hyperlipidemia produced by estrogen-progestin formulation. 207 Nov 84

The effects of exercise on plasma lipids and lipoproteins, high density lipoprotein (HDL) subclass cholesterol levels, and low density lipoprotein (LDL) subclass composition and metabolism were studied in Yucatan miniature swine following 2 yr of training. The exercise protocol produced significant training effects. Post-heparin lipolytic activity was also significantly increased. Although plasma cholesterol and triglycerides did not differ significantly (P = 0.08) between the exercised and control groups, multivariate analysis indicated a strong association between lipoprotein lipase (LPL) and HDL2-C (P less than 0.0001). Although HDL-C levels rose only slightly (P less than 0.09) with exercise, a significant shift was noted in the distribution of cholesterol from the HDL3 to the HDL2 fractions, perhaps mediated by the substantial increase in LPL activity. Exercise had little effect on the chemical composition of the major lipoprotein classes; however, the triglyceride content of the lighter LDL1 subclass was significantly reduced. In the more dense LDL2 subclass, exercise resulted in a significant decrease in triglycerides concomitant with a significant increase in free cholesterol levels. In contrast with the small reductions in fractional catabolic rates (FCR) in either subclass, production rates of the exercised group were reduced, which accounted for the reduction in LDL subclass pool size. These data indicate that exercise produces subtle but significant changes in lipoprotein metabolism that have been previously associated with reduced risk of atherosclerosis.
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PMID:The effect of exercise on plasma lipids and LDL subclass metabolism in miniature swine. 207 33

Hepatic, heparin-releaseable lipase is a multifunctional enzyme that may act on all lipoprotein classes present in plasma from fasted subjects. Recent evidence suggests that the enzyme also plays a role in the metabolism of chylomicronremnants. Its activity is impaired in normolipidemic patients with coronary heart disease, which also have a delayed removal of chylomicronremnants from plasma. Therefore hepatic lipase, in addition to lipoprotein lipase, plays an important role in postprandial lipoprotein metabolism. The activity levels of lecithin: cholesterol acyltransferase (LCAT) and cholesterylester transfer protein (CETP) are virtually unchanged after the ingestion of an oral fat load by normolipidemic subjects. However, the net mass transfer of cholesterylesters out of HDL into apo B-containing lipoproteins (chylomicronremnants, VLDL/IDL/LDL) is strongly increased. All triglyceride-rich lipoprotein fractions accumulate postprandially and, as a result of CETP action, become enriched in cholesterylesters. Defects in hepatic remnant removal may result in influx of remnants into the arterial wall. In patients with hyperlipidemia (and increased risk for atherosclerosis) the CETP-mediated formation of cholesterylester-rich remnants may operate, not only during the postprandial phase, but continuously.
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PMID:[Role of hepatic lipases, cholesterol ester transfer proteins and LCAT in the postprandial phase]. 208 75

This report describes the response of patients with severe coronary artery disease to a dynamic fat load test and monitors the change induced by fenofibrate therapy. The presence of disease was associated with prolonged and exaggerated hypertriglyceridemia following the meal and with lower basal HDL cholesterol and HDL subfraction masses. A further indicator of risk was the persistence of increased amounts of retinyl palmitate in the plasma of severely affected individuals 24 h after its ingestion with the meal. These observations are consistent with the proposal that the clearance of chylomicrons and their remnants is impaired in coronary atherosclerosis. Fenofibrate reduced alimentary lipemia following the fat load in both normo- and hypercholesterolemic subjects. This was associated with a 10% rise in plasma HDL cholesterol levels. The improvement in chylomicron catabolism probably derived from a 37% increase (P less than 0.001) in lipoprotein lipase activity induced by fenofibrate. Hepatic lipase on the other had was only slightly affected by treatment.
Atherosclerosis 1990 Dec
PMID:Postprandial lipemia, fenofibrate and coronary artery disease. 210 83

Lipoprotein lipase (LPL) (EC 3.1.1.34) hydrolyzes triacylglycerols of very low density lipoproteins and chylomicrons. It is produced by several cell types, including macrophages, which are frequent in atherosclerotic lesions. The atherosclerotic plaque also contains activated T lymphocytes. We therefore investigated the possible regulatory effect of the T lymphocyte-derived lymphokine interferon-gamma (IFN-gamma) on macrophage LPL. Human monocyte-derived macrophages were treated with recombinant IFN-gamma or conditioned medium from activated peripheral blood mononuclear cells for 3 days. LPL activity was thereafter measured in the culture medium and in cell homogenates. The enzyme protein was detected at a cellular level by immunocytochemistry and immunopredicipitation. Recombinant IFN-gamma caused a profound decrease in macrophage LPL secretion. The IFN-gamma-treated cells, however, still contained immunodetectable enzyme and the decrease in secretion was apparently only partly due to an inhibited synthesis. Conditioned medium from activated peripheral blood mononuclear cells also drastically decreased the macrophage LPL secretion. When the conditioned medium was treated with antibodies against IFN-gamma, its down-regulating effect on macrophage LPL was totally removed. The data indicate that IFN-gamma is inhibiting macrophage LPL at least in part via a reduction of LPL synthesis. A local release of IFN-gamma may be important in the pathogenesis of atherosclerosis by affecting the lipid accumulation in the lesion.
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PMID:Interferon-gamma inhibits lipoprotein lipase in human monocyte-derived macrophages. 211 81


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