TY - JOUR
T1 - Effects of lovastatin on the levels, structure, and atherogenicity of VLDL in patients with moderate hypertriglyceridemia
AU - Gianturco, Sandra H.
AU - Bradley, William A.
AU - Nozaki, Shuichi
AU - Vega, Gloria L
AU - Grundy, Scott M
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1993
Y1 - 1993
N2 - 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 Sr 100-400 and Sr 60-100 but not Sr 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 Sr 100-400 and VLDL Sr 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 Sr 100-400 after lovastatin was 32%, similar to the 34% average decrease in cholesteryl ester content of VLDL Sr 100-400 after lovastatin. Although statistical significance was not achieved, there was a trend toward decreased VLDL Sr 100-400-induced rapid, receptor-mediated triglyceride accumulation in P388Dr macrophages after lovastatin. Taken together, these observations sueeest that lovastatin mav he of potential benefit in decreasing the atherosclerotic complications of hypertriglyceridemia.
AB - 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 Sr 100-400 and Sr 60-100 but not Sr 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 Sr 100-400 and VLDL Sr 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 Sr 100-400 after lovastatin was 32%, similar to the 34% average decrease in cholesteryl ester content of VLDL Sr 100-400 after lovastatin. Although statistical significance was not achieved, there was a trend toward decreased VLDL Sr 100-400-induced rapid, receptor-mediated triglyceride accumulation in P388Dr macrophages after lovastatin. Taken together, these observations sueeest that lovastatin mav he of potential benefit in decreasing the atherosclerotic complications of hypertriglyceridemia.
KW - Atherosclerosis
KW - Foam cells
KW - Hypertriglyceridemia
KW - LDL receptor
KW - Lovastatin
KW - Triglyceride-rich lipoproteins
KW - VLDL
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M3 - Article
C2 - 8385478
AN - SCOPUS:0027457353
SN - 1079-5642
VL - 13
SP - 472
EP - 481
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 4
ER -