Published online before print November 13, 2003, doi: 10.1161/01.ATV.0000105904.02142.e7
© 2004 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Leptin Promotes Vascular Remodeling and Neointimal Growth in Mice
From the Department of Cardiology and Pulmonary Medicine (K.S., M.H., C.G., M.P., S.K.), University of Goettingen, Goettingen, Germany, and the Department of Cell Biology (C.D., D.J.L.), Division of Vascular Biology, The Scripps Research Institute, La Jolla, Calif.
Correspondence to Stavros Konstantinides, MD, Department of Cardiology and Pulmonary Medicine, Georg August University of Goettingen, Robert Koch Strasse 40, D-37075 Goettingen, Germany. E-mail skonstan{at}med.uni-goettingen.de
Objectives— Human obesity is associated with elevated leptin levels and a high risk of death from cardiovascular disease. In the present study, we investigated the effects of leptin on vascular wound healing and arterial lesion growth in mice.
Methods and Results— Wild-type mice placed on an atherogenic, high-fat diet had elevated (9-fold) leptin levels compared with their counterparts maintained on normal chow, and the former demonstrated significantly enhanced neointimal thickening after carotid artery injury with ferric chloride. The lesions forming in response to injury strongly expressed leptin receptor mRNA and protein. Unexpectedly, the atherogenic diet had no effect on injured vessels from leptin-deficient ob/ob mice despite aggravating obesity, diabetes, and hyperlipidemia in these animals. Daily administration of leptin to ob/ob mice during the 3-week period after injury reversed this phenotype, dramatically increasing neointimal thickness and the severity of luminal stenosis. Exogenous leptin also enhanced lesion growth and increased cellular proliferation in injured arteries from wild-type mice but had no effect on vessels from leptin receptor–deficient db/db mice.
Conclusions— Our results raise the possibility that there might be a direct, leptin receptor-mediated link between the hyperleptinemia in human obesity and the increased risk for cardiovascular complications associated with this condition.
Key Words: leptin • obesity • neointima
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