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Leptin Enhances Neointimal Formation Following Vascular Injury through Effects on the Vessel Wall
Author(s) -
Shen Yuechun,
Bodary Peter F.,
Vargas Fernando B.,
Wickenheiser Kevin J.,
Eitzman Daniel T.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a205-a
Subject(s) - leptin , neointima , medicine , leptin receptor , endocrinology , neointimal hyperplasia , restenosis , obesity , stent
Leptin is a risk factor for cardiovascular disease, although the mechanism by which leptin increases this risk is unknown. We hypothesized that leptin may contribute to vascular disease through effects on vascular remodeling. A mouse model of arterial injury was used that induces endothelial damage followed by intimal hyperplasia. Femoral arterial injury was induced in wild type ( WT ) (n=10), leptin deficient ( Lep ob/ob ) (n=13), and leptin receptor deficient ( Lepr db/db ) (n=16) mice. Four weeks after injury, the mean neointimal area of Lep ob/ob and Lepr db/db mice was 0.005±0.001 and 0.007±0.002 mm 2 , which was reduced compared to WT mice (0.011±0.003 mm 2 ) ( P <0.009 and <0.02, respectively). Leptin replacement studies were performed on Lep ob/ob mice using either intraperitoneal recombinant murine leptin or intravenous adenovirusexpressing murine leptin (ad‐leptin). Both strategies of leptin replacement produced enhanced neointimal formation (recombinant murine leptin, 0.015 ±0.004; ad‐leptin, 0.037±0.002 mm 2 ) compared to Lep ob/ob mice not receiving leptin replacement ( P <0.001 for both). The neointima of Lepr db/db mice receiving ad‐leptin was not different from control Lepr db/db mice. To determine the cellular compartment responsible for the leptin effect on neointimal formation, bone marrow transplantation was performed from Lepr db/db to WT mice. No difference on neointima was observed, implicating components of the vessel wall as the relevant leptin target. These observations demonstrate that mice lacking leptin or the leptin receptor are protected from neointimal formation following vascular injury and suggest that leptin may play a role in vascular disease by promoting lesion growth through direct effects on the vessel wall.