Leptin promotes neointimal formation by stimulating vascular smooth muscle cell proliferation through leptin receptor
10.3760/cma.j.issn.0253-3758.2009.07.017
- VernacularTitle:瘦素通过其受体刺激小鼠血管平滑肌细胞增殖而促进动脉内膜增生
- Author:
Yue-Chun SHEN
1
;
Zhao-Chu HE
;
Dong-Feng LU
;
Bi-Ru OU
;
Jie-Zhen PAN
;
Xiao-Ming WANG
;
Jun LI
Author Information
1. 广州医学院附属第一医院
- Keywords:
Atherosclerosis;
Leptin;
Tunica intima
- From:
Chinese Journal of Cardiology
2009;37(7):634-638
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of leptin in neointimal formation and related mechanisms.Methods Femoral arterial injury was induced in wild-type (Wt,n = 10),leptin-deficient (Lep -/-,n = 12),and ieptin receptor-deficient (LepR -/- ,n = 10) mice.Leptin treatment studies (tail vein injection of adenovirus expressing murine ieptin on the RSV promoter,ad-leptin) were performed on Lep -/- (n = 5) and LepR -/- (n = 4) mice.Intimal (I) and medial (M) areas were measured and the ratio of I/M was calculated.Smooth muscle cells were detected by smooth muscle α-actin staining using an α-actin monoclonal antibody.Cellular proliferation was analyzed with BrdU Staining Kit and the number of BrdU-positive cells was counted manually.Plasma leptin level was measured by ELISA.Results The I/M ratio of Lep -/- and LepR -/- mice was significantly lower than that in Wt separately (Lep -/- vs.Wt = 0.80±0.14 vs.1.50±0.22,P<0.01; LepR-/- vs.Wt=0.55±0.20 vs.1.50±0.22,P<0.05).Plasma leptin level was significantly increased in Lep-/- and LepR -/- mice post leptin treatment.I/M was significantly increased in Lep -/- mice receiving ad-leptin compared with untreated Lep -/- mice (P < 0.05),while I/M was similar between LepR -/- mice with and without ad-leptin treatment (P > 0.05).The changes on number of positive α-actin and BrdU stained smooth muscle cells were consistent with the neointimal formation findings in various groups.Conclusions Mice lacking leptin or the ieptin receptor were protected from neointimal formation following vascular injury.Leptin treatment increased neointimsl formation in Lep-/- but not in LepR-/- mice,suggesting leptin receptor activation and vascular smooth muscle cell proliferation played a pivotal role on neointimal formation post-injury in this model,giving an evidence that high plasma leptin level is a risk factor for neointimal formation.
