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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1256.)
© 2001 American Heart Association, Inc.

Editorials

Statins Inhibit Leukocyte Recruitment

New Evidence for Their Anti-Inflammatory Properties

Brenda R. Kwak; François Mach

From the Division of Cardiology, Foundation for Medical Research, University Hospital, Geneva Medical School, Geneva, Switzerland.

Correspondence to François Mach, MD, Cardiology Division, Foundation for Medical Research, 64 Avenue Roseraie, 1211 Geneva 4, Switzerland. E-mail machf@cmu.unige.ch

Key Words: Editorials • inflammation • statins • leukocytes

Atherosclerosis and its devastating clinical complications, such as arterial thrombosis; ischemia and infarction of the heart, brain, and other vital organs; ruptured aortic aneurysms; and peripheral vascular insufficiency, continue to account for the majority of morbidity and mortality in the adult population of industrialized nations.¹ The process of atherosclerosis is not simply an inevitable degenerative consequence of aging in the large arteries but a progressive disease characterized by chronic inflammation.^2–4 Increasing evidence suggests that atherosclerosis is a multifactorial process involving the interplay of lipid metabolism, mononuclear leukocytes, coagulation proteins, cytokines, extracellular matrix, and hemodynamic forces.⁵ Since their introduction in the late 1980s, statins have revolutionized the treatment of dyslipidemia and demonstrated their ability to reduce and prevent coronary morbidity and mortality in both primary and secondary intervention trials.⁶ Statins competitively inhibit 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme crucial to cholesterol biosynthesis. The resulting decrease in hepatic cholesterol concentration leads to a compensatory increase in expression of hepatic LDL receptors, which clear cholesterol-rich LDL and LDL precursors from the circulation. However, mevalonate, the product of HMG-CoA reductase, is the precursor not only for cholesterol but also for many nonsteroidal isoprenoid compounds. The isoprenoids farnesyl pyrophosphate and geranylgeranyl pyrophosphate are known to play an important role in signal transduction pathways by their attachment to signaling proteins, such as Ras and Rho.⁷

See p 1165 and 1327

The effectiveness and rapidity with which statins decrease coronary events already led a few years ago to the speculation that statins might influence vascular biology . . . [Full Text of this Article]

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