© 2001 American Heart Association, Inc.
Editorial |
New Evidence for Beneficial Effects of Statins Unrelated to Lipid Lowering
From the Department of Medicine, University of California, San Diego.
Correspondence to Wulf Palinski, MD, University of California, San Diego, Department of Medicine, 0682, 9500 Gilman Dr, MTF 110, La Jolla, CA 92093-0682. E-mail wpalinski@ucsd.edu
Key Words: HMG-CoA inhibitors • chronic and acute inflammation • atherosclerosis • immune system • in vivo
Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) constitute the single most powerful class of hypolipidemic drugs currently available. Their efficacy in reducing coronary morbidity and mortality has been established by several large secondary and primary intervention trials (reviewed in Reference 11 ). Remarkably, in some of these trials, survival curves began to diverge within a relatively short period, presumably too short to achieve a significant reduction of preexisting atheroma2 or to prevent progression of lesions to clinically relevant stages. This suggests that effects of statins other than lesion regression contribute to the rapid reduction of coronary symptoms.
During the past several years, numerous additional effects of
statins on vascular cells have been identified that could modulate
atherogenesis, plaque rupture, or thrombosis. Some of these appear to
be independent of cholesterol
lowering.3 4 For
example, statins upregulate nitric oxide (NO) expression by interfering
with the posttranscriptional regulation of endothelial
NO synthase
(eNOS).5 6 Evidence
for the importance of this mechanism in vivo was provided by the
observation that statins inhibit ischemic cerebral stroke
induced by occlusion of the middle cerebral artery in normal but not in
eNOS-deficient mice.7 Other
potentially protective effects of statins on
endothelial cells include an increased fibrinolytic
activity through enhanced expression of tissue plasminogen
activator and platelet activator
inhibitor-1.8 In
smooth muscle cell cultures, statins inhibit
proliferation9 and stimulate
apoptosis.10
Monocyte recruitment into the vascular intima in response to
inflammatory cytokines may also be affected by statins, which
inhibit the expression of monocyte chemotactic protein-1 by stimulated
peripheral
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