title: Effect of simvastatin on trioleylglycerol hydrolysis and transacylation with cholesterol in serum of outpatients with coronary heart disease.
abstract: At present, the most effective drugs in treating hypercholesterolemia and atherosclerosis are the statins, which are potent inhibitors of the rate-limiting enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Serum triacylglycerol (TAG) levels associate positively with the risk for coronary heart disease (CHD). Triacylglycerols are mainly hydrolyzed by the enzyme lipase (glycerol ester hydrolase [GEH], EC 3.1.1.3) but can also be transformed by transacylation with cholesterol (glycerol ester:cholesterol acyltransferase [GECAT], EC 2.3.1.43). We evaluated the effect of a 3-month treatment with simvastatin (10 mg/day) on GEH and GECAT activity in the serum of 26 outpatients with CHD. The activity of both GEH and GECAT was reduced in the CHD group compared with that in the control group: 5.9 +/- 0.9 mU/mg vs. 7.5 +/- 1.8 mU/mg and 11.1 +/- 1.4 mU/mg vs. 19.3 +/- 3.3 mU/mg, respectively (p < or = 0.05). In addition to the well known effect of reducing total cholesterol and low-density lipoprotein cholesterol in patients with CHD, we observed two other results of simvastatin treatment. First, GEH activity increased to values similar to those found in healthy subjects and, simultaneously, GECAT activity decreased. Trioleylglycerol transacylation with cholesterol amounted to 72% and hydrolysis to 28% in the control group and to 65% and 35% in the CHD group, respectively. After simvastatin treatment, transacylation with cholesterol and hydrolysis amounted to 51% and 49%, respectively. In conclusion, by increasing GEH and reducing GECAT, simvastatin seems not only to affect cholesterol synthesis but also to alter triacylglycerol metabolism. Further studies are needed to determine the physiological significance of these changes and their relationship with the development of atherosclerosis.
authors.affiliation: Lipid Metabolism Laboratory, Department of General Chemistry, University of Medical Sciences, 6 Grunwaldzka St., PL 60-780 Poznan, Poland. stolzmar@am.poznan.pl
authors.forename: M
authors.initials: M
authors.lastname: Pioruńska-Stolzmann
authors.forename: A
authors.initials: A
authors.lastname: Pioruńska-Mikolajczak
authors.forename: Z
authors.initials: Z
authors.lastname: Mikolajczyk
mesh_terms: D000215:Acylation; D000293:Adolescent; D000328:Adult; D000368:Aged; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D003327:Coronary Disease / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D014304:Triolein / Q000378:metabolism*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D014304:Triolein; D002784:Cholesterol; D019821:Simvastatin; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D008049:Lipase