Cholesterol lowering and endothelial function

被引:110
作者
Vogel, RA [1 ]
机构
[1] Univ Maryland, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21201 USA
关键词
D O I
10.1016/S0002-9343(99)00261-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The pathophysiology of the association between cholesterol and atherosclerosis has been thought to involve the deposition, modification, and cellular uptake of cholesterol. We now believe that the process begins with vascular injury and involves inflammation and vessel remodeling. The vascular endothelium actively regulates vascular tone, lipid breakdown, thrombogenesis, inflammation, and vessel growth, all of which are important factors in the development of atherosclerosis. Endothelial dysfunction promotes atherosclerosis through vasoconstriction, monocyte and platelet adhesion, thrombogenesis, and cytokine and growth factor stimulation and release. An important component of endothelial dysfunction is reduced availability of nitric oxide, which is caused by low-density lipoproteins, especially if they are oxidized. This reduced availability appears to occur through a combination of decreased production, abnormal signaling, and increased destruction by oxygen-free radicals. Concurrently, endothelium-mediated vasoconstrictors, adhesion molecules, cytokines, growth factors, and thrombogenic factors, such as endothelin, are increased by oxidized low-density lipoprotein. Several studies have shown improvements in endothelial function with cholesterol lowering, which may explain the early and substantial reductions in major cardiovascular events associated with cholesterol lowering. Am J Med. 1999;107:479-487. (C) 1999 by Excerpta Medica, Inc.
引用
收藏
页码:479 / 487
页数:9
相关论文
共 122 条
[31]   CORONARY PLAQUE DISRUPTION [J].
FALK, E ;
SHAH, PK ;
FUSTER, V .
CIRCULATION, 1995, 92 (03) :657-671
[32]   Coronary plaque erosion without rupture into a lipid core - A frequent cause of coronary thrombosis in sudden coronary death [J].
Farb, A ;
Burke, AP ;
Tang, AL ;
Liang, YH ;
Mannan, P ;
Smialek, J ;
Virmani, R .
CIRCULATION, 1996, 93 (07) :1354-1363
[33]  
FLAVAHAN NA, 1990, BLOOD VESSELS, V27, P218
[34]   FLOW EFFECTS ON PROSTACYCLIN PRODUCTION BY CULTURED HUMAN-ENDOTHELIAL CELLS [J].
FRANGOS, JA ;
ESKIN, SG ;
MCINTIRE, LV ;
IVES, CL .
SCIENCE, 1985, 227 (4693) :1477-1479
[35]   HELSINKI HEART-STUDY - PRIMARY-PREVENTION TRIAL WITH GEMFIBROZIL IN MIDDLE-AGED MEN WITH DYSLIPIDEMIA - SAFETY OF TREATMENT, CHANGES IN RISK-FACTORS, AND INCIDENCE OF CORONARY HEART-DISEASE [J].
FRICK, MH ;
ELO, O ;
HAAPA, K ;
HEINONEN, OP ;
HEINSALMI, P ;
HELO, P ;
HUTTUNEN, JK ;
KAITANIEMI, P ;
KOSKINEN, P ;
MANNINEN, V ;
MAENPAA, H ;
MALKONEN, M ;
MANTTARI, M ;
NOROLA, S ;
PASTERNACK, A ;
PIKKARAINEN, J ;
ROMO, M ;
SJOBLOM, T ;
NIKKILA, EA .
NEW ENGLAND JOURNAL OF MEDICINE, 1987, 317 (20) :1237-1245
[36]   THE OBLIGATORY ROLE OF ENDOTHELIAL-CELLS IN THE RELAXATION OF ARTERIAL SMOOTH-MUSCLE BY ACETYLCHOLINE [J].
FURCHGOTT, RF ;
ZAWADZKI, JV .
NATURE, 1980, 288 (5789) :373-376
[37]   MECHANISMS OF DISEASE - THE PATHOGENESIS OF CORONARY-ARTERY DISEASE AND THE ACUTE CORONARY SYNDROMES .1. [J].
FUSTER, V ;
BADIMON, L ;
BADIMON, JJ ;
CHESEBRO, JH .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 326 (04) :242-250
[38]   ROLE OF PLATELETS AND THROMBOSIS IN CORONARY ATHEROSCLEROTIC DISEASE AND SUDDEN-DEATH [J].
FUSTER, V ;
STEELE, PM ;
CHESEBRO, JH .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1985, 5 (06) :B175-B184
[39]   IMPAIRMENT OF ENDOTHELIUM-DEPENDENT DILATION IN RABBIT RENAL-ARTERIES BY OXIDIZED LIPOPROTEIN(A) - ROLE OF OXYGEN-DERIVED RADICALS [J].
GALLE, J ;
BENGEN, J ;
SCHOLLMEYER, P ;
WANNER, C .
CIRCULATION, 1995, 92 (06) :1582-1589
[40]   EVIDENCE THAT ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH HYPERCHOLESTEROLEMIA IS NOT DUE TO INCREASED EXTRACELLULAR NITRIC-OXIDE BREAKDOWN BY SUPEROXIDE ANIONS [J].
GARCIA, CE ;
KILCOYNE, CM ;
CARDILLO, C ;
CANNON, RO ;
QUYYUMI, AA ;
PANZA, JA .
AMERICAN JOURNAL OF CARDIOLOGY, 1995, 76 (16) :1157-1161