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

In vitro cholesteryl synthesis from oleic acid [1-14C] was studied with enzyme preparations from human thoracic aorta and liver. Results from studies on the properties of the esterifying system provide good evidence that the mechanism involves fatty acyl-CoA-cholesterol acyl transferase. In studies on human thoracic aorta with varying degrees of atherosclerotic disease, and pairs of normal and diseased aorta from the same subject, there was no obvious relationship between aortic cholesteryl esterifying activity and severity of atheroma. Normal aorta from two young males, presumably free of atherosclerosis, had relatively very low esterifying activity. In the six liver samples tested, there was negligible esterifying activity, in contrast to the high activity seen in the case of rat liver. For the thin layer chromatographic isolation of the labeled cholesteryl oleate a solvent system of isooctane:diethyl ether (100:6) was found to give a better separation of the ester than the petroleum ether: diethylether:acetic acid system generally used.
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PMID:Studies on cholesterol esterification in human tissues. 2 46

The metabolic effects of an acute acetate load have been investigated in chronic uremic patients and in controls. The decay rate of blood acetate levels was significantly lower in patients than in controls. Higher levels of blood acetoacetate and 2-oxoglutarate and plasma triglycerides were observed in the patients after the load. No difference was detectable in plasma levels of unesterified fatty acids and cholesterol between the two groups of subjects. Acetate oxidation in citric acid cycle may be reduced in uremia owing to a lack of coenzyme A. These observations raise the possibility that chronic acetate administration with the dialysate induces hypertriglyceridemia and accelerates the development of atherosclerosis in hemodialysis patients.
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PMID:Acetate intolerance in chronic uremic patients. 50 62

Low density lipoprotein (LDL) is routinely isolated and stored in buffers containing ethylene-diaminetetra-acetic acid (EDTA) to inhibit its autoxidation. We have investigated the effect of EDTA on LDL oxidation by both copper ions and macrophages. LDL oxidation by macrophages in Ham's F-10 medium containing 6 microM iron showed a large and concentration-dependent increase when EDTA was added up to about 10 microM. EDTA concentrations above about 10 microM progressively inhibited LDL oxidation as measured by macrophage degradation, thiobarbituric acid-reactive substances and electrophoretic mobility. The oxidation of LDL by 1 microM copper in Ham's F-10 medium, measured by macrophage degradation, also showed a large increase with low concentrations of EDTA (1-3 microM), with higher concentrations (10 microM or above) strongly inhibiting the oxidation. In a simple phosphate buffer, however, EDTA simply inhibited the oxidation of LDL by copper with equimolar amounts of EDTA to copper giving a complete inhibition. The results of this study indicate that when LDL oxidation by cells or by copper in Ham's F-10 medium is investigated, more oxidation may be obtained if the EDTA is not previously removed from the LDL preparation.
Atherosclerosis 1992 May
PMID:The effect of EDTA on the oxidation of low density lipoprotein. 163 57

Fibroblasts from patients with homozygous familial hypercholesterolemia (FH), a disease characterized by accelerated atherogenesis, are known to lack functional low-density-lipoprotein receptors, which ultimately results in increased cholesterol biosynthesis in the cultured cells. [14C]Acetate incorporation in these cells was compared to that of normal fibroblasts and to fibroblasts from patients with Down's syndrome, a disease in which atherosclerosis is rare. Total [14C]acetate incorporation did not differ significantly between normal and Down's fibroblasts, nor did its partitioning into the hexane-extractable and aqueous fractions of the cell hydrolysates. [14C]Acetate incorporation was much greater in FH cells in both the aqueous and hexane-extractable fractions. Preincubation in fetal bovine serum increased acetate incorporation only by FH cells, while 50 micrograms low-density lipoprotein/ml medium depressed acetate incorporation in all three groups. A C27 sterol, identified by gas chromatography-mass spectrometry as a probable isomer of cholesterol, was present in small amounts in FH fibroblasts, but was not detectable in the normal or Down's cells. The absolute amounts of [14C]acetate incorporated into the non-sterol lipids were greater in the FH fibroblasts, indicating that these cells may have to synthesize, in addition to cholesterol, other required cellular lipids which are delivered to the normal cells by low-density lipoproteins.
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PMID:[14C]acetate incorporation by cultured normal, familial hypercholesterolemia and Down's syndrome fibroblasts. 296 64

In previous studies, it was shown that a lysine deficient diet reduces the severity of aortic cholesterol atherosclerosis in rabbits. Feeding 1-amino-3-imino N,N' propene diacetate (AIPD) produced 2 metabolic by products with active aldehyde groups 1-amino propenal acetic acid (APA) and malonyldialdehyde (MDA) that transiently block the lysine epsilon-amino groups of all proteins and lipoproteins in vivo. This paper reports the effects of blocking the lysine free epsilon-amino groups of all lipoproteins on 2 different types of cholesterol atherosclerosis; (1) A proliferative-type cholesterol atherosclerosis containing a high proportion of spindle-shaped myogenic foam cells rich in collagen and alcian blue-stainable material produced by feeding a diet containing cholesterol, peanut oil, ethanol and butylated hydroxyanisole and (2) cholesterol atherosclerosis containing a high proportion of polyhedral-shaped nonmyogenic macrophage-type foam cells produced by feeding cholesterol and oleic acid. After 14 weeks on the diets the mean +/- SD percent of intimal aortic area covered with the myogenic-type atherosclerosis in the control peanut oil-fed group was 34 +/- 6% and this was reduced to 13 +/- 3% in the peanut oil AIPD group. In contrast, after 14 weeks in the control oleic acid group the severity of atherosclerosis was 14 +/- 4% and this was increased to 36 +/- 7% in the oleic acid AIPD group. Aortic cholesterol concentration was decreased in the AIPD peanut oil group relative to its control but was increased in the AIPD oleic acid group relative to its control group. A higher concentration of AIPD metabolites accumulated in the atherosclerotic lesions of the oleic AIPD group than in the peanut oil AIPD group indicating that a larger amount of lysine blocked lipoprotein accumulated in the macrophage-rich lesions of the oleic acid AIPD group than in the myogenic-rich lesions of the peanut oil AIPD group. Blocking lysine epsilon-amino groups in vivo by feeding AIPD did not modify DNA synthesis in the aortae of either AIPD group relative to their control groups.
Atherosclerosis 1985 Oct
PMID:Modification of two types of cholesterol atherosclerosis in rabbits by blocking lipoprotein lysine epsilon-amino groups. 393 26

The effect of AY-25,712 (2-methyl-2-phenyl-3(2H)-furanone-5-carboxylic acid) on serum lipids, hepatic lipogenesis and biliary cholesterol was investigated in male rats. Based on one-week treatment, the minimal effective dose of AY-25,712 which lowered serum triglycerides was 1 mg/kg/day, and LDL-cholesterol, 5 mg/kg/day. Nicotinic acid produced a similar lipid-lowering profile albeit at 5 times higher doses. AY-25,712 at doses of 2 mg/kg/day and higher significantly increased the ratio of HDL to total cholesterol. Unlike clofibrate, AY-25,712 did not increase liver weight or liver mitochondrial alpha-glycerophosphate dehydrogenase, nor increase biliary cholesterol levels in rats fed a diet containing 2% cholesterol and 0.5% cholic acid. AY-25,712 lowered serum cholesterol, triglycerides and phospholipids in rats rendered hyperlipidemic with Triton WR-1339 and decreased the elevated serum triglycerides in streptozotocin-diabetic rats. [14C]Acetate incorporation into cholesterol by liver homogenate was suppressed in rats given AY-25,712 p.o. for 1 week. The results show that AY-25,712 is a potent LDL-cholesterol- and triglyceride-lowering agent in rats, and that its lipid-lowering profile differs from that of clofibrate but resembles that of nicotinic acid.
Atherosclerosis 1982 Dec
PMID:Evaluation of the lipid-lowering activity of AY-25,712 in rats. 681 76

KC-9432 (a new hypolipidemic compound, alpha-[p-(p-chlorobenzoyl) phenoxy-alpha-cyclohexyl acetic acid ethyl ester) was studied in rats for its effect on plasma lipid and lipoprotein levels. KC-9432 was particularly effective in hyperlipidemia in rats fed with a diet containing 2% cholesterol and 1% sodium cholate. The hypocholesterolemic activity of KC-9432 was far more potent than that of clofibrate. KC-9432 markedly increased the reduced HDL cholesterol level in dietary-induced hyperlipidemia in rats.
Atherosclerosis 1980 Sep
PMID:Effect of KC-9432, a new hypolipidemic compound, on high density lipoprotein cholesterol in rats. 689 50

We previously reported that oleic acid (OA) rapidly increased apolipoprotein (apo) B secretion by suppressing early intracellular degradation of nascent apo B in Hep G2 cells and suggested that the suppression of apo B degradation is associated with triglyceride (TG) biosynthesis from OA. To determine whether the inhibition of apo B degradation is associated with increased TG synthesis or is a direct effect of OA, we examined the effect of another fatty acid, eicosapentoenoic acid (EPA), on apo B kinetics in Hep G2 cells, since it is well known to have hypolipidemic action in clinical studies. The incorporation of [3H]glycerol into cellular TG was stimulated five-fold when Hep G2 cells were incubated for 2 h with EPA or OA (0.4 or 0.8 mM-1.5% bovine serum albumin (BSA) complex). The incorporation of [14C]acetic acid into cellular cholesteryl ester (CE) was significantly decreased by EPA treatment, whereas OA did not affect CE synthesis. Similar effects of these fatty acids on cellular lipid synthesis were observed in long-term incubation (24 h). Apo B was linearly secreted into the medium during 3 h, and EPA and OA doubled the rate of secretion. In long-term (24 h) incubations, both fatty acids significantly increased the incorporation of [3H]leucine into secreted apo B radioactivity or the accumulation of apo B mass in the medium. Pulse-chase studies revealed that both EPA and OA reduced intracellular apo B degradation to a similar degree. The inhibition of apo B degradation was also observed when the cells were preincubated with either EPA or OA for 24 h. These results suggest that increased TG synthesis leads to suppression of intracellular apo B degradation, which is independent of the source of exogenous fatty acid.
Atherosclerosis 1995 Jan 06
PMID:Similar to oleic acid, eicosapentaenoic acid stimulates apolipoprotein B secretion by inhibiting its intracellular degradation in Hep G2 cells. 777 67

Proliferation of bovine aortic smooth muscle cells (SMCs) induced by thrombin, basic fibroblast growth factor, or serum is inhibited by anionic, nonsulfated aromatic compounds that mimic many of the effects of heparin. Among these compounds are aurintricarboxylic acid (ATA) and a newly synthesized polymer of 4-hydroxyphenoxy acetic acid (compound RG-13577). Iodinated- or 14C-labeled compound RG-13577 binds to cultured SMCs in a highly specific and saturable manner. Scatchard analysis of the binding data revealed the presence of an estimated 1 x 10(7) binding sites per cell with an apparent dissociation constant of 3 x 10(-6) mol/L. Binding of radiolabeled RG-13577 was efficiently competed for by related aromatic anionic compounds and by apolipoprotein E, but not by heparin, heparan sulfate, suramin, or various purified growth factors and extracellular matrix proteins. Receptor cross-linking of SMC-bound 125I-RG-13577 revealed a single species of high M(r) (approximately 280 kD) cell surface receptors detected in the absence but not the presence of excess unlabeled compound RG-13577. Binding was susceptible to downregulation and restoration of receptor levels in a manner similar to that of hormone and growth factor receptors. We suggest that the antiproliferative activity of compound RG-13577 and related compounds is initiated by binding to specific growth-inhibiting cell surface receptors. Heparin-mimicking compounds may be applied to inhibit SMC proliferation associated with atherosclerosis and restenosis.
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PMID:Antiproliferative activity to vascular smooth muscle cells and receptor binding of heparin-mimicking polyaromatic anionic compounds. 798 Nov 90

The effect of experimentally induced atherosclerosis on the synthesis and secretion of lipoproteins in the density range of very low density lipoproteins (VLDL) and low density lipoproteins (LDL) have been studied using primary cultures of rat hepatocytes. Rats fed atherogenic diet showed higher levels of lipids associated with serum VLDL and LDL fraction, aorta and liver when compared with animals fed normal diet. Incorporation of [3H]leucine into apo B associated with the cell layer and secreted by hepatocytes from rats fed atherogenic diet was significantly more when compared with normal hepatocytes. [14C]Acetate incorporation studies showed that the synthesis of cholesterol was lower in hepatocytes from atherogenic diet fed rats, but more of the newly synthesised cholesterol was found in the secreted VLDL; secretion of lipids, particularly triglycerides, unesterified cholesterol and cholesterol in the lipoproteins in the density range of VLDL and LDL was significantly more in these hepatocytes. The relative distribution of [3H]-radioactivity in the LDL density range was 57% in hepatocytes from atherogenic diet fed animals as compared with 28% in controls, suggesting a relatively higher production of lipoproteins in the LDL density range than VLDL by these cells. These results indicate that the hypercholesterolemia in atherogenic diet fed animals may among other factors be caused by increased synthesis of apo B by liver cells and resultant increase in the secretion of apo B containing lipoproteins.
Atherosclerosis 1993 Apr
PMID:Synthesis and secretion of apo B containing lipoproteins by primary cultures of hepatocytes isolated from rats fed atherogenic diet. 831 65


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