title: Pioglitazone modulates the proliferation and apoptosis of vascular smooth muscle cells via peroxisome proliferators-activated receptor-gamma.
abstract: BACKGROUND
  PPARγ is a member of the nuclear hormone receptor superfamily. It has been considered as a mediator regulating metabolism, anti-inflammation, and pro-proliferation in the Vascular Smooth Muscle Cells (VSMCs). Thiazolidinediones (TZDs), synthetic ligands of PPARγ, have anti-proliferative and pro-apoptotic effects on VSMCs, which prevent the formation and progression of atherosclerosis and restenosis following percutaneous coronary intervention (PCI). However, the underlying mechanism remains elusive. This present study therefore aimed to investigate the signaling pathway by which pioglitazone, one of TZDs, inhibits proliferation and induces apoptosis of VSMCs.
  
  
  METHODS
  The effects of pioglitazone on VSMC proliferation and apoptosis were studied. Cell proliferation was determined using BrdU incorporation assay. Cell apoptosis was monitored with Hoechst and Annexin V staining. The expression of caspases and cyclins was determined using real-time PCR and Western blot.
  
  
  RESULTS
  Pioglitazone treatment and PPARγ overexpression inhibited proliferation and induced apoptosis of VSMCs, whereas blocking by antagonist or silencing by siRNA of PPARγ significantly attenuated pioglitazone's effect. Furthermore, pioglitazone treatment or PPARγ overexpression increased caspase 3 and caspase 9 expression, and decreased the expression of cyclin B1 and cyclin D1 in VSMCs.
  
  
  CONCLUSIONS
  Pioglitazone inhibits VSMCs proliferation and promotes apoptosis of VSMCs through a PPARγ signaling pathway. Up-regulation of caspase 3 and down-regulation of cyclins mediates pioglitazone's anti-proliferative and pro-apoptotic effects. Our results imply that pioglitazone prevents the VSMCs proliferation via modulation of caspase and cyclin signaling pathways in a PPARγ-dependent manner.
authors.affiliation: Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Cardiology, Tongji Medical College of Huazhong University of Science and Technology affiliated Tongji Hospital, Wuhan, Hubei China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei China.
authors.forename: Shengping
authors.initials: S
authors.lastname: Chao
authors.affiliation: Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei China.
authors.forename: Shixi
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Gan
authors.affiliation: Department of Cardiology, Tongji Medical College of Huazhong University of Science and Technology affiliated Tongji Hospital, Wuhan, Hubei China.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Cardiology, Tongji Medical College of Huazhong University of Science and Technology affiliated Tongji Hospital, Wuhan, Hubei China.
authors.forename: Chang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Tongji Medical College of Huazhong University of Science and Technology affiliated Tongji Hospital, Wuhan, Hubei China.
authors.forename: Yexin
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Cardiovascular Research, Life Science and Technology College, Human Genome Research Center, Huazhong University of Science and Technology, Wuhan, Hubei China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tu
keywords: Apoptosis; Caspase; Cyclins; Peroxisome proliferators-activated receptor gamma; Thiazolidinedione