This Article Full Text Full Text (PDF) All Versions of this Article: 25/8/e119    most recent 01.ATV.0000173306.47722.ecv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bodary, P. F. Articles by Eitzman, D. T. Search for Related Content PubMed PubMed Citation Articles by Bodary, P. F. Articles by Eitzman, D. T.

(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

This article has been cited by other articles:

				N. Sattar, G. Wannamethee, N. Sarwar, J. Chernova, D. A. Lawlor, A. Kelly, A. M. Wallace, J. Danesh, and P. H. Whincup Leptin and coronary heart disease: prospective study and systematic review. J. Am. Coll. Cardiol., January 13, 2009; 53(2): 167 - 175. [Abstract] [Full Text] [PDF]

				F. Dol-Gleizes, R. Paumelle, V. Visentin, A.-M. Mares, P. Desitter, N. Hennuyer, A. Gilde, B. Staels, P. Schaeffer, and F. Bono Rimonabant, a Selective Cannabinoid CB1 Receptor Antagonist, Inhibits Atherosclerosis in LDL Receptor-Deficient Mice Arterioscler. Thromb. Vasc. Biol., January 1, 2009; 29(1): 12 - 18. [Abstract] [Full Text] [PDF]

				M. R. Schroeter, M. Leifheit, P. Sudholt, N.-M. Heida, C. Dellas, I. Rohm, F. Alves, M. Zientkowska, S. Rafail, M. Puls, et al. Leptin Enhances the Recruitment of Endothelial Progenitor Cells Into Neointimal Lesions After Vascular Injury by Promoting Integrin-Mediated Adhesion Circ. Res., August 29, 2008; 103(5): 536 - 544. [Abstract] [Full Text] [PDF]

				B. K. Surmi, R. D. Atkinson, M. L. Gruen, K. R. Coenen, and A. H. Hasty The role of macrophage leptin receptor in aortic root lesion formation Am J Physiol Endocrinol Metab, March 1, 2008; 294(3): E488 - E495. [Abstract] [Full Text] [PDF]

				S. Taleb, O. Herbin, H. Ait-Oufella, W. Verreth, P. Gourdy, V. Barateau, R. Merval, B. Esposito, K. Clement, P. Holvoet, et al. Defective Leptin/Leptin Receptor Signaling Improves Regulatory T Cell Immune Response and Protects Mice From Atherosclerosis Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2691 - 2698. [Abstract] [Full Text] [PDF]

				P. F. Bodary Links Between Adipose Tissue and Thrombosis in the Mouse Arterioscler. Thromb. Vasc. Biol., November 1, 2007; 27(11): 2284 - 2291. [Abstract] [Full Text] [PDF]

				R. J. Westrick, M. E. Winn, and D. T. Eitzman Murine Models of Vascular Thrombosis Arterioscler. Thromb. Vasc. Biol., October 1, 2007; 27(10): 2079 - 2093. [Abstract] [Full Text] [PDF]

				R. Yang and L. A. Barouch Leptin Signaling and Obesity: Cardiovascular Consequences Circ. Res., September 14, 2007; 101(6): 545 - 559. [Abstract] [Full Text] [PDF]

				D. M. Shih, Y.-R. Xia, X.-P. Wang, S. S. Wang, N. Bourquard, A. M. Fogelman, A. J. Lusis, and S. T. Reddy Decreased Obesity and Atherosclerosis in Human Paraoxonase 3 Transgenic Mice Circ. Res., April 27, 2007; 100(8): 1200 - 1207. [Abstract] [Full Text] [PDF]

				A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]