title: Olmesartan ameliorates pressure overload-induced cardiac remodeling through inhibition of TAK1/p38 signaling in mice.
abstract: OBJECTIVE
  Many studies have demonstrated the potent effects of ARB administration on heart failure. However, the mechanism of the potent effects of ARB on cardiac remodeling is less well understood. We investigated the role of Olmesartan on the fibrosis and hypertrophy in mouse heart.
  
  
  METHODS
  We employed TAC surgery, a mouse model of chronic cardiac failure. All the mice were separated into three groups: the sham group, TAC group and TAC plus Olmesartan group (given Olmesartan treatment after TAC). We analyzed left ventricle remodeling, and function by echocardiography or pathology. We further detected the level of marker genes involved in fibrosis and hypertrophy and in cultured neonatal rat cardiac fibroblasts and myocytes infected by constitutively active TAK1 and p38MAPK. After TAC, all the mice developed hypertrophy, worse cardiac function and malignant remodeling in left ventricle.
  
  
  RESULTS
  Olmesartan improved heart remodeling and function without changing pressure of blood. Moreover, Olmesartan reduced the level of transforming growth factor β activated kinase-1 (TAK1) and phospho-p38MAPK. In neonatal rat cardiac fibroblast cells and cardiomyocytes, Olmesartan also decreased TAK1 and p38MAPK activation triggered by TGFβ1 or AngII. The inhibitory effect of Olmesartan was abrogated by overexpression of constitutively active TAK1 and p38MAPK by adenovirus system.
  
  
  CONCLUSIONS
  Our results suggest Olmesartan improves heart remodeling and function induced by pressure overload. P38MAPK inactivation attenuated by olmesartan via inhibition of TAK1 pathway plays an important role in the process.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou 325027, Zhejiang, China; Department of Cardiology, The First Affiliated Hospital of Suzhou University, 188 Shizi Road, Suzhou 215006, Jiangsu, China.
authors.forename: Lianpin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Oral Prophylaxis and Hygiene, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chong
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Yinqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Yuechun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Maoping
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Suzhou University, 188 Shizi Road, Suzhou 215006, Jiangsu, China. Electronic address: three.stonee@gmail.com.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006321:Heart / Q000187:drug effects*; D007093:Imidazoles / Q000627:therapeutic use*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013777:Tetrazoles / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D020930:MAP Kinase Kinase Kinases; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases; D000099151:MAP Kinase Kinase Kinase 7; C437965:olmesartan
keywords: Cardiac fibrosis; Cardiac remodeling; Olmesartan; Transforming growth factor β activated kinase-1; Transverse aorta constriction