Effects of lovastatin on the levels, structure, and atherogenicity of VLDL in patients with moderate hypertriglyceridemia.
The purpose of this study was to determine whether lovastatin treatment reduced very low density lipoprotein (VLDL) abnormalities in hypertriglyceridemic subjects. Lovastatin reduced plasma triglyceride levels and the levels of total VLDL, intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) cholesterol. The numbers of VLDL particles of Sf 100-400 and Sf 60-100 but not Sf 20-60 particles were reduced by lovastatin, as was the amount of cholesteryl ester per particle. All VLDL subspecies bound to the LDL receptor of cultured human fibroblasts with similar, high affinities on both placebo and lovastatin, but VLDL Sf 100-400 and VLDL Sf 60-100 caused less suppression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase activity after lovastatin therapy, indicating reduced LDL receptor-mediated cholesterol delivery. The average decrease in reductase suppression by VLDL Sf 100-400 after lovastatin was 32%, similar to the 34% average decrease in cholesteryl ester content of VLDL Sf 100-400 after lovastatin. Although statistical significance was not achieved, there was a trend toward decreased VLDL Sf 100-400-induced rapid, receptor-mediated triglyceride accumulation in P388D1 macrophages after lovastatin. Taken together, these observations suggest that lovastatin may be of potential benefit in decreasing the atherosclerotic complications of hypertriglyceridemia.
University of Alabama, Birmingham 35294-0012.
S H
SH
Gianturco
W A
WA
Bradley
S
S
Nozaki
G L
GL
Vega
S M
SM
Grundy
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000209:etiology*; D002784:Cholesterol / Q000097:blood; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000378:metabolism; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000378:metabolism; D018110:Receptors, Lipoprotein; D014280:Triglycerides / Q000097:blood
D008055:Lipids; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; D014280:Triglycerides; D002784:Cholesterol; D008148:Lovastatin