title: [Angiotensin-converting enzyme 2 gene transfer attenuates neointimal formation after carotid artery ischemia-reperfusion injury in rats].
abstract: OBJECTIVE
  To explore the effects of lentiviral recombinant angiotensin-converting enzyme 2 (LV-ACE2) gene transfer on the neointimal formation after carotid artery ischemia-reperfusion injury (IRI) and related mechanisms.
  
  
  METHODS
  IRI was induced in SD rats through the carotid artery clipping and rats were divided into IRI, IRI+LV-GFP, IRI+LV-ACE2, IRI+ paclitaxel groups (n = 10 each). Sham operated rats serve as normal control. Four weeks later, neointimal formation was observed on HE stained carotid artery sections. The protein expression of ACE2, α-SM-actin, CD31, AT1R and P-ERK were detected by immunohistochemistry.
  
  
  RESULTS
  (1) Carotid artery neointimal hyperplasia was readily shown in IRI group [I/M: 1.517 ± 0.151 (4 weeks later) vs. 0.011 ± 0.004 (Sham), P < 0.01], which was significantly reduced in IRI+LV-ACE2 (0.71 ± 0.17) and IRI+ paclitaxel (0.89 ± 0.21) groups. (2) The growth of vascular smooth muscle cells and neovascularization were also significantly inhibited in IRI+LV-ACE2 group and the expression of α-SM-actin (5 843 ± 839 vs. 12 648 ± 1 760, P < 0.01) and CD31 [(12.40 ± 4.01)/mm(2) vs. (96.20 ± 17.79)/mm(2), P < 0.01], AT1R (1 219 ± 175 vs. 4 861 ± 545, P < 0.01) and P-ERK1/2 phosphorylation (1 040 ± 215 vs. 2 938 ± 286, P < 0.01) in the neointimal of the injury arteries in IRI+LV-ACE2 group were significantly downregulated compared to IRI group.
  
  
  CONCLUSIONS
  This data suggest that ACE2 gene overexpression is able to attenuate neointimal formation after ischemia-reperfusion injury possibly through downregulating AT1 receptor expression and signal pathway of ERK1/2 phosphorylation.
authors: Department of Cardiology, First Affiliated Hospital, Fujian Medical University, Hypertension Research Division, Fuzhou 350005, China.
authors: Xu-wei
authors: XW
authors: Wu
authors: Department of Cardiology, First Affiliated Hospital, Fujian Medical University, Hypertension Research Division, Fuzhou 350005, China.
authors: Zhuo-qiang
authors: ZQ
authors: Lu
authors: Department of Cardiology, First Affiliated Hospital, Fujian Medical University, Hypertension Research Division, Fuzhou 350005, China.
authors: Jing-jing
authors: JJ
authors: Gong
authors: Department of Cardiology, First Affiliated Hospital, Fujian Medical University, Hypertension Research Division, Fuzhou 350005, China.
authors: Hua-jun
authors: HJ
authors: Wang
authors: Department of Cardiology, First Affiliated Hospital, Fujian Medical University, Hypertension Research Division, Fuzhou 350005, China.
authors: Chang-sheng
authors: CS
authors: Xu
authors: Department of Cardiology, First Affiliated Hospital, Fujian Medical University, Hypertension Research Division, Fuzhou 350005, China. Email: jxueqing@sohu.com.
authors: Xue-qing
authors: XQ
authors: Jin
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D017536:Carotid Artery, Common / Q000473:pathology*; D018014:Gene Transfer Techniques; D020935:MAP Kinase Signaling System; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D058426:Neointima / Q000473:pathology*; D009389:Neovascularization, Pathologic; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2