title: Valsartan decreases neointimal hyperplasia in balloon-injured rat aortic arteries by upregulating HO-1 and inhibiting angiotensin II type 1 receptor.
abstract: OBJECTIVE
  Upregulation of heme oxygenase (HO)-1 plays an important role in vascular protection. Valsartan attenuates neointimal hyperplasia in animal studies. The objective of this study was to examine the role of HO-1 and angiotensin II type 1 (AT1) receptor in the action of valsartan on neointimal hyperplasia in balloon-injured rat aortic arteries.
  
  
  METHODS
  Thirty-six male Wistar rats were randomly divided into the following three groups with twelve rats in each group: control group, surgery (model) group, and valsartan group. Aortic balloon injury was performed to elicit endothelial denudation with a 2F balloon catheter. On days 14 and 28 after injury, blood was harvested to measure bilirubin levels. Aortic arteries were harvested for morphometry analysis, to determine angiotensin II (Ang II) level, and to analyze mRNA or protein expression.
  
  
  RESULTS
  Compared with the control group, proliferation and intimal thickening of vascular smooth muscle cells (VSMCs) were obvious in the surgery group rats on days 14 and 28 after injury. Valsartan significantly reduced the proliferation and intimal thickening. Additionally, pretreatment with valsartan significantly reduced Ang II levels, AT1 receptor, and p38 mitogen-activated protein kinase (MAPK) expression. Valsartan increased HO-1 protein and mRNA expression, as well as increased serum bilirubin levels compared with the surgery group.
  
  
  CONCLUSIONS
  Valsartan treatment decreased neointimal hyperplasia in balloon-injured rats. The mechanism of action might be linked to the upregulation of HO-1, downregulation of AT1 receptor and inhibition of p38MAPK signal pathway.
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Hypertension Laboratory, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Qixin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Qingke
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Shanglang
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Emergency, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Emergency, Qingdao's Municipal Hospital, Qingdao 266003, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Ren
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Tingru
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China. Electronic address: liyonghong-66@163.com.
authors.forename: Haichu
authors.initials: H
authors.lastname: Yu
mesh_terms: D000704:Analysis of Variance; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology*; D001663:Bilirubin / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006965:Hyperplasia / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D058426:Neointima / Q000188:drug therapy / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D017931:DNA Primers; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000068756:Valsartan; D051547:Heme Oxygenase-1; D014633:Valine; D001663:Bilirubin
keywords: Angiotensin II type 1 receptor; Balloon injury; Heme oxygenase-1; Valsartan; p38 mitogen-activated protein kinase