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Submitted on September 14, 2006
Accepted on October 31, 2006
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.
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