title: Effects of rosuvastatin on expression of angiotensin-converting enzyme 2 after vascular balloon injury in rats.
abstract: OBJECTIVE
  To investigate the effects and mechanisms of rosuvastatin on angiotensin -converting enzyme 2 (ACE2) in the process of neointimal formation after vascular balloon injury in rats, and to explore the effects of ACE2 and rosuvastatin in restenosis.
  
  
  METHODS
  Thirty-six Wistar rats were randomly allocated into three groups: control group (n = 12), surgery group (n = 12), and statin group (n = 12). Aortic endothelial denudation of rats was performed using 2F balloon catheters. At days 14 and 28 after injury, aortic arteries were harvested to examine the following. Intimal thickening was examined by hematoxylin and eosin staining. We measured angiotensin II (Ang II) and angiotensin 1-7 (Ang-[1-7]) levels by a radioimmunological method or enzyme-linked immunosorbent assay. Protein and mRNA expression of ACE2 and Ang II type 1 receptor (AT1) were investigated by immunohistochemistry, Western blots, and Reverse transcriptase-polymerase chain reaction (RT-PCR). We measured changes in proliferating cell nuclear antigen (PCNA) by immunohistochemistry. The level of phosphorylated extracellular signal regulated kinase 1/2 (P-ERK1/2) was evaluated by Western blotting.
  
  
  RESULTS
  Proliferation of vascular smooth muscle cells (VSMC) and intimal thickening were higher at day 14 after vascular balloon injury in the surgery group compared with the control group. Proliferation of VSMC was decreased by day 28 after injury, while intimal thickening continued. With rosuvastatin treatment, the extent of VSMC proliferation and intimal thickening was reduced at day 14 and 28 after injury. Ang II and P-ERK levels were significantly increased, Ang-(1-7) levels were significantly decreased, mRNA and protein expressions of ACE2 were significantly decreased, and AT1 expression was significantly increased at days 14 and 28 after vascular balloon injury in the surgery group compared with the control group. PCNA expression was higher in the surgery group than in the control group, and it was significantly decreased after being given rosuvastatin. Expression of ACE2 mRNA and protein, and Ang-(1-7) levels were significantly increased, while AT1 expression and levels of Ang II and P-ERK were significantly decreased in the statin group compared with the surgery group.
  
  
  CONCLUSIONS
  Expression of ACE2 mRNA and protein is decreased in the process of intimal thickening after balloon injury. The inhibitory effect of rosuvastatin on intimal thickening is related to upregulation of ACE2, an increase in Ang-(1-7), downregulation of AT1, and activation of the P-ERK pathway.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Qi-Xin
authors.initials: QX
authors.lastname: Wang
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Zhou
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Chu
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Man
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Ren
authors.forename: Ting-Ru
authors.initials: TR
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: An
keywords: Angiotensin converting enzyme 2; Balloon injury; Extracellular signal regulated kinase; Rosuvastatin