Cellular and molecular mechanisms of statins: an update on pleiotropic effects.
Coronary artery disease (CAD) is the leading cause of death worldwide. The efficacy and safety of statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) in primary and secondary prevention of CAD are confirmed in several large studies. It is well known that statins have some pleiotropic, anti-atherosclerotic effects. We review the molecular mechanisms underlying the beneficial effects of statins revealed in recently published studies. Endothelial cell injury is regarded as the classic stimulus for the development of atherosclerotic lesions. In addition, the inflammatory process plays an important role in the aetiology of atherosclerosis. In particular, chronic inflammation plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. Our previous reports and others have demonstrated beneficial effects of statins on endothelial dysfunction and chronic inflammation in CAD. A better understanding of the molecular mechanism underlying the effectiveness of statins against atherosclerosis may provide a novel therapeutic agent for the treatment of coronary atherosclerosis. The present review summarizes the cellular and molecular mechanism of statins against coronary atherosclerosis.
*Division of Biomedical Information Analysis, Institute for Biomedical Sciences, Iwate Medical University, Iwate, Japan.
Mamoru
M
Satoh
†Division of Cardiology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
Yuji
Y
Takahashi
‡Division of Cardioangiology, Nephrology and Endocrinology, Iwate Medical University School of Medicine, Iwate, Japan.
Tsuyoshi
T
Tabuchi
‡Division of Cardioangiology, Nephrology and Endocrinology, Iwate Medical University School of Medicine, Iwate, Japan.
Yoshitaka
Y
Minami
‡Division of Cardioangiology, Nephrology and Endocrinology, Iwate Medical University School of Medicine, Iwate, Japan.
Makiko
M
Tamada
†Division of Cardiology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
Kan
K
Takahashi
†Division of Cardiology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
Tomonori
T
Itoh
†Division of Cardiology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
Yoshihiro
Y
Morino
‡Division of Cardioangiology, Nephrology and Endocrinology, Iwate Medical University School of Medicine, Iwate, Japan.
Motoyuki
M
Nakamura
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D008055:Lipids / Q000097:blood; D035683:MicroRNAs / Q000378:metabolism; D011322:Primary Prevention / Q000379:methods*; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects; D016615:Telomere / Q000378:metabolism; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D008055:Lipids; D035683:MicroRNAs