title: [Leptin promotes neointimal formation by stimulating vascular smooth muscle cell proliferation through leptin receptor].
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 leptin receptor-deficient (LepR(-)/-, n = 10) mice. Leptin treatment studies (tail vein injection of adenovirus expressing murine leptin 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 alpha-actin staining using an alpha-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 alpha-actin and BrdU stained smooth muscle cells were consistent with the neointimal formation findings in various groups.
  
  
  CONCLUSIONS
  Mice lacking leptin or the leptin receptor were protected from neointimal formation following vascular injury. Leptin treatment increased neointimal 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.
authors: Department of Cardiology, First Affiliated Hospital, Guangzhou Medical College, Guangzhou 510120, China.
authors: Yue-chun
authors: YC
authors: Shen
authors: Zhao-chu
authors: ZC
authors: He
authors: Dong-feng
authors: DF
authors: Lu
authors: Bi-ru
authors: BR
authors: Ou
authors: Jie-zhen
authors: JZ
authors: Pan
authors: Xiao-ming
authors: XM
authors: Wang
authors: Jun
authors: J
authors: Li
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D049109:Cell Proliferation; D020738:Leptin / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D054411:Receptors, Leptin / Q000378:metabolism; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D000199:Actins; D020738:Leptin; D054411:Receptors, Leptin