TY - JOUR
T1 - Lovastatin therapy in familial dysbetalipoproteinemia
T2 - Effects on kinetics of apolipoprotein B
AU - Vega, Gloria L
AU - East, Cara
AU - Grundy, Scott M
N1 - Funding Information:
The authors express appreciation to Biman Pramanik, Carolyn Croy, Peggy Loessberg, Rosemary Abate, Cynthia Stenoien, Elisa Heyrich, Raymond Wheatley and Marjorie Whelan for excellent technical assistance. We thank Dr. William F. Beltz for consultation and assistance in kinetic modeling. Also the participation of the nursing and dietetic staff of the General Clinical Research Center of Parkland Memorial Hospital and the metabolic unit of the Veterans Administration Medical Center, Dallas, Texas is gratefully acknowledged. This work was supported by the
PY - 1988/3
Y1 - 1988/3
N2 - Familial dysbetalipoproteinemia is characterized by hyperlipidemia, increases in beta-migrating, very low density lipoproteins (β-VLDL), and homozygosity for apolipoprotein E2 (apo E2). In this study, 3 patients with familial dysbetalipoproteinemia were treated with lovastatin, and kinetics for apolipoprotein B (apo B) were determined in control and drug treatment periods. Multicompartmental analyses of apo B kinetics in VLDL and in low density lipoproteins (LDL) were carried out. Lovastatin therapy generally lowered plasma concentrations of apo B and cholesterol in VLDL and LDL. The reductions in concentrations were due mainly to a decrease in transport (production) rates for these fractions. Indeed, the fractional clearance rate (FCR) for LDL-apo B was reduced during lovastatin therapy. The decreased transport rate for VLDL-apo B and LDL-apo B could have been due to an inhibition of the synthesis of lipoproteins containing apo B. An alternate explanation is that lovastatin promoted direct removal of a rapidly-catabolized fraction of VLDL-apo B that is a precursor for longer-lived lipoproteins in the circulation; this mechanism could decrease input rates of identifiable lipoprotein species and retard their clearance because of "saturation" of LDL receptors by more rapidly removed lipoproteins. Finally, both mechanisms, i.e., decreased production and increased clearance of lipoproteins, may have contributed to the fall in VLDL-apo B and LDL-apo B concentrations during lovastatin therapy.
AB - Familial dysbetalipoproteinemia is characterized by hyperlipidemia, increases in beta-migrating, very low density lipoproteins (β-VLDL), and homozygosity for apolipoprotein E2 (apo E2). In this study, 3 patients with familial dysbetalipoproteinemia were treated with lovastatin, and kinetics for apolipoprotein B (apo B) were determined in control and drug treatment periods. Multicompartmental analyses of apo B kinetics in VLDL and in low density lipoproteins (LDL) were carried out. Lovastatin therapy generally lowered plasma concentrations of apo B and cholesterol in VLDL and LDL. The reductions in concentrations were due mainly to a decrease in transport (production) rates for these fractions. Indeed, the fractional clearance rate (FCR) for LDL-apo B was reduced during lovastatin therapy. The decreased transport rate for VLDL-apo B and LDL-apo B could have been due to an inhibition of the synthesis of lipoproteins containing apo B. An alternate explanation is that lovastatin promoted direct removal of a rapidly-catabolized fraction of VLDL-apo B that is a precursor for longer-lived lipoproteins in the circulation; this mechanism could decrease input rates of identifiable lipoprotein species and retard their clearance because of "saturation" of LDL receptors by more rapidly removed lipoproteins. Finally, both mechanisms, i.e., decreased production and increased clearance of lipoproteins, may have contributed to the fall in VLDL-apo B and LDL-apo B concentrations during lovastatin therapy.
KW - Apolipoproteinemia B
KW - Dysbetalipoproteinemia
KW - Lovastatin
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U2 - 10.1016/0021-9150(88)90107-4
DO - 10.1016/0021-9150(88)90107-4
M3 - Article
C2 - 3162680
AN - SCOPUS:0023880277
SN - 0021-9150
VL - 70
SP - 131
EP - 143
JO - Atherosclerosis
JF - Atherosclerosis
IS - 1-2
ER -