on November 9, 2006
Published online before print November 9, 2006, doi: 10.1161/01.ATV.0000252068.89775.ee
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Submitted on September 14, 2006
Accepted on October 31, 2006
Leptin Regulates Neointima Formation After Arterial Injury Through Mechanisms Independent of Blood Pressure and the Leptin Receptor/STAT3 Signaling Pathways Involved in Energy Balance
Peter F. Bodary ;
From the Divisions of Cardiovascular Medicine and Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
* To whom correspondence should be addressed. E-mail: deitzman{at}umich.edu.
Background--Leptin is an adipocyte-derived hormone critical for energy homeostasis and implicated in vascular disease processes. The relevant cellular leptin receptor pools and signaling pathways involved in leptin-related vascular phenotypes in vivo are unclear.
Methods and Results--Arterial injury was induced in wild-type (wt), leptin-deficient (lepob/ob), and leptin receptor-deficient (leprdb/db) mice. Compared with wt mice, lepob/ob and leprdb/db mice were protected from the development of neointima. Bone marrow transplantation experiments between wt and leprdb/db mice indicated that the vascular protection in leprdb/db mice was not attributable to lack of leptin receptor expression on bone marrow-derived elements. To investigate the role of the lepr-mediated signal transducer and activator of transcription 3 (STAT3) signaling pathway in the response to vascular injury, leprs/s mice homozygous for a leptin receptor defective in STAT3 signaling underwent femoral arterial injury. Despite similar obesity and blood pressure levels, the neointimal area in leprs/s mice was significantly increased compared with leprdb/db mice.
Conclusions--The molecular mechanism by which the leptin receptor mediates neointima formation and vascular smooth muscle cell proliferation is largely independent of the STAT3-dependent signaling pathways involved in energy balance.
Key words: atherosclerosis • obesity • remodeling • restenosis
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