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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:e119.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Recombinant Leptin Promotes Atherosclerosis and Thrombosis in Apolipoprotein E–Deficient Mice

Peter F. Bodary; Shufang Gu; Yuechun Shen; Alyssa H. Hasty; Joshua M. Buckler; Daniel T. Eitzman

From the Department of Internal Medicine (P.F.B., S.G., Y.S., J.M.B., D.T.E.), Division of Cardiovascular Medicine, University of Michigan Medical Center, Ann Arbor; and the Department of Molecular Physiology and Biophysics and Medicine (A.H.H.), Vanderbilt University, Nashville, Tenn.

Correspondence to Daniel T. Eitzman, MD, 1150 W Medical Center Dr, 7301 MSRB III, Ann Arbor, MI 48109-0644. E-mail deitzman{at}umich.edu

Objective— The direct role of leptin in vascular disease remains controversial. The objective of this study was to examine the effects of leptin treatment on atherosclerosis and thrombosis in atherosclerotic-prone mice.

Methods and Results— Sixteen-week-old, male apolipoprotein E–deficient mice were treated with injections of recombinant leptin (125 µg per day IP; n=10) or vehicle (n=10) for 4 weeks. Leptin treatment resulted in reduced epididymal fat (352±30.7 versus 621±61.5 mg; P=0.005) and fasting insulin (0.57±0.25 versus 1.7±0.22 ng/mL; P=0.014). Despite these metabolic benefits, leptin treatment resulted in an increase in atherosclerosis (8.0±0.95% versus 5.4±0.59% lesion surface coverage; P<0.05). Leptin treatment also resulted in a shortened time to occlusive thrombosis after vascular injury (21±2.1 versus 34.6±5.4 minutes; P=0.045).

Conclusions— These studies indicate that exogenous leptin promotes atherosclerosis and thrombosis and support the concept that elevations of leptin may increase the risk for cardiovascular disease.

The direct role of leptin in vascular disease remains controversial. Our studies indicate that exogenous leptin promotes atherosclerosis and thrombosis and support the concept that elevations of leptin may increase the risk for cardiovascular disease.

Key Words: obesity • vascular smooth muscle • arterial injury • adipocyte • adipokines

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