on June 9, 2005
Published online before print June 9, 2005, doi: 10.1161/01.ATV.0000173306.47722.ec
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Submitted on March 30, 2005
Accepted on May 26, 2005
Recombinant Leptin Promotes Atherosclerosis and Thrombosis in Apolipoprotein E-Deficient Mice
Peter F. Bodary ;
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.
* To whom correspondence should be addressed. 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.
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