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)

Oxidized low-density lipoprotein (ox-LDL) plays an important role in the development of atherosclerosis and potentially influences the endothelial regulation of vasomotor tone. We have recently shown that lysophosphatidylcholine (LPC), a lysophospholipid contained in ox-LDL, has various pathophysiological effects. We further examined the role of LPC in the ox-LDL-induced vasoactivity in isolated pig coronary arteries. Copper-induced ox-LDL but not native LDL (n-LDL) elicited endothelium-dependent contraction during plateau contraction evoked by prostaglandin F2 alpha. Lipid extracted from ox-LDL (ox-LDL-lipid) also induced vasocontraction, but lipid of n-LDL (n-LDL-lipid) did not influence tone. When LPC was depleted from ox-LDL (i.e., defatted albumin- or phospholipase B-treated ox-LDL), vasocontraction was significantly attenuated. Synthetic palmitoyl LPC also induced endothelium-dependent vasocontraction, mimicking the response elicited by ox-LDL, but phosphatidylcholine, which exists in n-LDL and is converted to LPC during oxidative modification of LDL, did not influence the tone. Contraction to either ox-LDL or LPC was significantly attenuated by NG-monomethyl-L-arginine but not by indomethacin or superoxide dismutase. Forty minutes of incubation of coronary rings with either ox-LDL or LPC significantly attenuated endothelium-dependent vasorelaxation to thrombin without affecting vasorelaxation to endothelium-independent vasodilator nitroglycerin. In conclusion, LPC contained in lipid fraction of ox-LDL caused endothelium-dependent contraction and inhibited endothelium-dependent relaxation in isolated pig coronary arteries. The vasocontraction might be at least in part caused by LPC-mediated inhibition of endothelium-derived nitric oxide release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:LPC in oxidized LDL elicits vasocontraction and inhibits endothelium- dependent relaxation. 781 Jul 42

Human aortic extracts contain significant cholesteryl ester hydrolytic activity. The enzymic activity was shown to be activated by trihydroxylated bile salt, but not by dihydroxylated bile salt. Monospecific antibodies prepared against rat pancreatic carboxyl ester lipase (CEL, cholesterol esterase) immunoprecipitated cholesteryl ester hydrolytic activity from human aorta, demonstrating that the neutral CEL in aorta is highly similar to and probably identical with the pancreatic enzyme. Reverse transcriptase PCR amplification of mRNA from human aortic endothelial cells revealed de novo synthesis of the pancreatic-type CEL by these cells. Preincubating human aortic endothelial cells with oxidized or native low-density lipoprotein resulted in an 8- and 3-fold increase in CEL activity secreted into the culture medium respectively. A potential physiological role for the endothelial CEL was demonstrated by studies showing its ability to confer partial protection against the cytotoxic effects of lysophosphatidylcholine. The protective effect of CEL is related to its bile-salt-independent lysophospholipase activity. However, CEL hydrolysis of lysophosphatidylcholine can be inhibited by excess cholesterol. Taken together, these results indicate that pancreatic-type CEL is synthesized by cells lining the vessel wall. Moreover, vascular CEL may interact with cholesterol and oxidized lipoproteins to modulate the progression of atherosclerosis.
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PMID:Synthesis and secretion of the pancreatic-type carboxyl ester lipase by human endothelial cells. 944 98

Although White Carneau (WC) pigeons are known to be more susceptible to atherosclerosis than Show Racer (SR) pigeons, the reasons for this difference are not fully understood. While no major differences are known in the lipoprotein composition, a difference in the cholesteryl ester (CE) composition was reported. However, there is little information on the activity or specificity of lecithin:cholesterol acyltransferase (LCAT), the major source of plasma CE. In order to determine whether the esterification of cholesterol or other functions of LCAT are compromised in WC pigeons, we studied the various reactions catalyzed by LCAT in the two groups. The cholesterol esterification was found to be significantly lower in WC pigeons, whether assayed with exogenous or endogenous substrates. Furthermore, lyso phosphatidylcholine (PC) esterification and oxidized PC hydrolysis, two other reactions carried out by LCAT, were also lower in WC. We found evidence for the presence of an active lysophospholipase in pigeon plasma, and this activity was also lower in WC compared to SR. A significant increase in the FC/PC ratio, another reported atherogenic risk factor, was found in WC. plasma. Because of the absence of other hydrolytic enzymes in pigeon plasma, LCAT may play an important role in the metabolism of oxidized PC generated during lipoprotein oxidation, and therefore a decrease in its activity in White Carneau pigeons may contribute to increased risk of atherosclerosis.
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PMID:Impaired function of lecithin:cholesterol acyltransferase in atherosclerosis-susceptible White Carneau pigeons: possible effects on metabolism of oxidized phospholipids. 950 85

Pharmacological characterization of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl)ureido]methyl]cyclohexane), a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, was performed with both in vitro and in vivo assay systems. NTE-122 inhibited microsomal ACAT activities of various tissues (liver of rabbit and rat, small intestine of rabbit and rat, and aorta of rabbit) and cultured cells (HepG2 and CaCo-2), with IC50 values from 1.2 to 9.6 nM. The inhibition mode of NTE-122 was competitive for HepG2 ACAT. NTE-122 had no effect on other lipid metabolizing enzymes, such as 3-hydroxy-3-methylglutaryl-CoA reductase, acyl-CoA synthetase, cholesterol esterase, lecithin:cholesterol acyltransferase, acyl-CoA:sn-glycerol-3-phosphate acyltransferase and cholesterol 7alpha-hydroxylase up to 10 microM. When NTE-122 was administered to the cholesterol diet-fed rats, serum and liver cholesterol levels were markedly reduced with an ED50 of 0.12 and 0.44 mg/kg/day, respectively. In the cholesterol diet-fed rabbits, NTE-122 significantly lowered plasma and liver cholesterol levels at more than 2 mg/kg/day. These results indicate that NTE-122 is a potent, selective and competitive inhibitor of ACAT, making it a worth while therapeutic agent for hypercholesterolemia and atherosclerosis.
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PMID:Cholesterol-lowering effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on cholesterol diet-fed rats and rabbits. 986 70