Gene activation, apolipoprotein A-I high density lipoprotein, atherosclerosis prevention and longevity

被引:40
作者
Luoma, PV [1 ]
机构
[1] UNIV OULU, THULE INST, FIN-90220 OULU, FINLAND
来源
PHARMACOLOGY & TOXICOLOGY | 1997年 / 81卷 / 02期
关键词
D O I
10.1111/j.1600-0773.1997.tb00032.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Recent studies in man and human apolipoprotein A-I transgenic animals emphasize the significance of apolipoprotein A-I and high density lipoprotein in antiatherogenesis. Several drugs and other compounds, e.g. phenobarbital, gemfibrozil, fenofibrate, prednisone, estrogen and alcohol, induce apolipoprotein A-I synthesis. They commonly produce serum lipoprotein patterns typical of a low risk of coronary heart disease, and many of them have been found to prevent atherognesis, reduce coronary heart disease mortality and increase survival. These compounds act against atherosclerosis by using one or several mechanisms that include overexpression of the apolipoprotein A-I gene with an increase in serum apolipoprotein A-I and high density lipoprotein and promotion of reverse cholesterol transport, upregulation of the row density lipoprotein receptor gene with a decrease in serum apolipoprotein B and low density lipoprotein, maintenance of endothelial cell function and protection against thrombosis. They have been found to raise high density lipoprotein cholesterol and apolipoprotein A-I together with a decrease in cholesterol ester transfer protein activity, and to induce hepatic cholesterol 7 alpha-hydroxylase and cholesterol and bile acid elimination from the body. By raising the activities of apolipoprotein A-I/high density lipoprotein-associated paraoxonase and other antioxidative enzymes, the inducers have the capacity to prevent atherogenesis in arterial walls through inhibition of the oxidative modification of low density lipoprotein. Other antiatherogenic vascular actions of high density lipoprotein include interference with low density lipoprotein aggregation and uptake by endothelial cells, and competition with low density lipoprotein for endothelial-localized low density lipoprotein receptors. Apolipoprotein A-I/high density lipoprotein beneficially enhances fibrinolysis, decreases platelet aggregation, increases prostacyclin production and stabilization and prevents atherogenic immune and inflammatory responses. This gene activation or microsomal induction can prevent atherosclerosis and is a basis for tailoring effective new agents and optimal non-invasive therapy against atherosclerotic vascular disease, to promote health and enhance longevity.
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收藏
页码:57 / 64
页数:8
相关论文
共 71 条
[1]   ETHANOL STIMULATES APOLIPOPROTEIN A-I SECRETION BY HUMAN HEPATOCYTES - IMPLICATIONS FOR A MECHANISM FOR ATHEROSCLEROSIS PROTECTION [J].
AMARASURIYA, RN ;
GUPTA, AK ;
CIVEN, M ;
HORNG, YC ;
MAEDA, T ;
KASHYAP, ML .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1992, 41 (08) :827-832
[2]  
AVOGARO P, 1984, CLIN METABOLIC ASPEC, P289
[3]  
BADIMON JJ, 1992, CIRCULATION, V86, P86
[4]   REGRESSION OF ATHEROSCLEROTIC LESIONS BY HIGH-DENSITY-LIPOPROTEIN PLASMA FRACTION IN THE CHOLESTEROL-FED RABBIT [J].
BADIMON, JJ ;
BADIMON, L ;
FUSTER, V .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (04) :1234-1241
[5]   High density lipoproteins and coronary heart disease [J].
Barter, PJ ;
Rye, KA .
ATHEROSCLEROSIS, 1996, 121 (01) :1-12
[6]  
BONDJERS G, 1976, ARTERY, V2, P200
[7]   SYNTHESIS AND SECRETION OF APOLIPOPROTEIN-A-I [J].
CALANDRA, S ;
TARUGI, P .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1993, 21 (02) :493-499
[8]  
CAMPBELL AJ, 1993, J AM GERIATR SOC, V41, P1333
[9]  
CHAO YS, 1985, MOL PHARMACOL, V27, P394
[10]   EFFECT OF SIMVASTATIN ON HIGH-DENSITY-LIPOPROTEIN SUBFRACTIONS AND APOLIPOPROTEINS IN TYPE-IIA HYPERCHOLESTEROLEMIA [J].
CROOK, D ;
BRUCE, R ;
WORTHINGTON, M ;
MULCAHY, D ;
PATTERSON, D ;
WYNN, V .
CARDIOVASCULAR DRUGS AND THERAPY, 1992, 6 (06) :633-639