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Circulation Research. 2008;103:536-544
Published online before print July 24, 2008, doi: 10.1161/CIRCRESAHA.107.169375
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(Circulation Research. 2008;103:536.)
© 2008 American Heart Association, Inc.

Integrative Physiology

Leptin Enhances the Recruitment of Endothelial Progenitor Cells Into Neointimal Lesions After Vascular Injury by Promoting Integrin-Mediated Adhesion

Marco R. Schroeter, Maren Leifheit, Philipp Sudholt, Nana-Maria Heida, Claudia Dellas, Ilonka Rohm, Frauke Alves, Marta Zientkowska, Stavros Rafail, Miriam Puls, Gerd Hasenfuss, Stavros Konstantinides, Katrin Schäfer

From the Departments of Cardiology and Pulmonary Medicine (M.R.S., M.L., P.S., N.-M.H., C.D., I.R., S.R., M.P., G.H., S.K., K.S.) and Hematology and Oncology (F.A., M.Z.), Georg August University of Goettingen, Germany. Present address for S.R.: First Division of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece.

Correspondence to Katrin Schaefer, MD, Department of Cardiology and Pulmonary Medicine, University of Goettingen, Robert Koch Strasse 40, D-37099 Goettingen, Germany. E-mail katrin.schaefer{at}med.uni-goettingen.de

The adipocytokine leptin modulates vascular remodeling and neointima formation. Because endothelial progenitor cells (EPCs) participate in vascular repair, we analyzed the effects of leptin on human EPC function in vitro and in vivo. After 7 days in culture, EPCs expressed the leptin receptor and responded to leptin stimulation with increased STAT3 phosphorylation. Incubation of EPCs with leptin (at concentrations between 1 and 100 ng/mL) increased the number of EPCs adhering to vitronectin and fibronectin in a receptor-specific manner. It also enhanced the capacity of EPCs to incorporate into a monolayer of human endothelial cells and the adherence of these cells to activated platelets. Leptin upregulated {alpha}vβ5 and {alpha}4 integrin expression in EPCs, and the effects of leptin on EPC function could be prevented, at least in part, by RGD peptides and function-blocking antibodies. Intravenous injection of fluorescently labeled human EPCs into athymic nude mice shortly after vascular injury revealed that preincubation of EPCs with leptin augmented their accumulation within intimal lesions, accelerating reendothelialization and decreasing neointima formation in an {alpha}vβ5 and {alpha}4 integrin-dependent manner. Our findings suggest that leptin specifically modulates the adhesive properties and the homing potential of EPCs and may thus enhance their capacity to promote vascular regeneration in vivo.


Key Words: leptin • endothelial progenitor cells • neointima formation • integrins


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