Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability

被引:317
作者
Koh, KK [1 ]
机构
[1] Gachon Med Sch, Ctr Heart, Div Cardiol, Inchon 405760, South Korea
关键词
atherosclerosis; endothelial function; infection/inflammation; statins;
D O I
10.1016/S0008-6363(00)00146-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Clinical trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statin therapy demonstrate an improvement in cardiovascular end points and coronary stenosis. However, an improvement in cardiovascular end points and coronary stenosis is incompletely explained by the baseline or treated LDL cholesterol level. The beneficial effects of statins on clinical events may involve nonlipid mechanisms that modify endothelial function, smooth muscle cells, and monocyte-macrophage: vasomotor function, inflammatory responses, and plaque stability. Augmented bioactivity of NO by statin therapy either indirectly by its effect on lipoprotein Levels and protection of LDL from oxidation, or directly by effects on NO synthesis and release, might account for enhancement of endothelium-dependent vasodilation. Recent experimental and animal studies have demonstrated that statins dose-dependently decrease smooth muscle cells migration and proliferation, independently of their ability to reduce plasma cholesterol. Moreover, statins are able to reduce the in vitro cholesterol accumulation in macrophages and expression of matrix metalloproteinase, resulting in plaque stability. These effects of statins were completely prevented by the addition of mevalonate and partially by all-trails farnesol and all-trans geranylgeraniol, confirming the specific role of isoprenoid metabolites, probably through prenylated proteins, in regulating these cellular events. Statins have been shown to prevent the activation of monocytes into macrophages, inhibit the production of pro-inflammatory cytokines, C-reactive protein, and cellular adhesion molecules. Statins decrease the adhesion of monocyte to endothelial cells. Accordingly, statins exert their cardiovascular benefits through a direct antiatherogenic properties in the arterial wall, beyond their effects on plasma lipids. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:648 / 657
页数:10
相关论文
共 104 条
  • [1] Soluble cell adhesion molecules in hypertriglyceridemia and potential significance on monocyte adhesion
    Abe, Y
    El-Masri, B
    Kimball, KT
    Pownall, H
    Reilly, CF
    Osmundsen, K
    Smith, CW
    Ballantyne, CM
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1998, 18 (05) : 723 - 731
  • [2] Aengevaeren WRM, 1997, CIRCULATION, V96, P429
  • [3] Lipid lowering promotes accumulation of mature smooth muscle cells expressing smooth muscle myosin heavy chain isoforms in rabbit atheroma
    Aikawa, M
    Rabkin, E
    Voglic, SJ
    Shing, H
    Nagai, R
    Schoen, FJ
    Libby, P
    [J]. CIRCULATION RESEARCH, 1998, 83 (10) : 1015 - 1026
  • [4] Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma - A potential mechanism of lesion stabilization
    Aikawa, M
    Rabkin, E
    Okada, Y
    Voglic, SJ
    Clinton, SK
    Brinckerhoff, CE
    Sukhova, GK
    Libby, P
    [J]. CIRCULATION, 1998, 97 (24) : 2433 - 2444
  • [5] ANGIOGRAPHIC PROGRESSION OF CORONARY-ARTERY DISEASE AND THE DEVELOPMENT OF MYOCARDIAL-INFARCTION
    AMBROSE, JA
    TANNENBAUM, MA
    ALEXOPOULOS, D
    HJEMDAHLMONSEN, CE
    LEAVY, J
    WEISS, M
    BORRICO, S
    GORLIN, R
    FUSTER, V
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1988, 12 (01) : 56 - 62
  • [6] Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection -: The azithromycin in coronary artery disease:: Elimination of myocardial infection with Chlamydia (ACADEMIC) study
    Anderson, JL
    Muhlestein, JB
    Carlquist, J
    Allen, A
    Trehan, S
    Nielson, C
    Hall, S
    Brady, J
    Egger, M
    Horne, B
    Lim, T
    [J]. CIRCULATION, 1999, 99 (12) : 1540 - 1547
  • [7] THE EFFECT OF CHOLESTEROL-LOWERING AND ANTIOXIDANT THERAPY ON ENDOTHELIUM-DEPENDENT CORONARY VASOMOTION
    ANDERSON, TJ
    MEREDITH, IT
    YEUNG, AC
    FREI, B
    SELWYN, AP
    GANZ, P
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (08) : 488 - 493
  • [8] REGRESSION OF CORONARY ATHEROMATOSIS IN RHESUS MONKEYS
    ARMSTRONG, ML
    WARNER, ED
    CONNOR, WE
    [J]. CIRCULATION RESEARCH, 1970, 27 (01) : 59 - +
  • [9] HMG-CoA reductase inhibitors reduce MMP-9 secretion by macrophages
    Bellosta, S
    Via, D
    Canavesi, M
    Pfister, P
    Fumagalli, R
    Paoletti, R
    Bernini, F
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1998, 18 (11) : 1671 - 1678
  • [10] Direct vascular effects of HMG-CoA reductase inhibitors
    Bellosta, S
    Bernini, F
    Ferri, N
    Quarato, P
    Canavesi, M
    Arnaboldi, L
    Fumagalli, R
    Paoletti, R
    Corsini, A
    [J]. ATHEROSCLEROSIS, 1998, 137 : S101 - S109