title: Aliskiren Inhibits Neointimal Matrix Metalloproteinases in Experimental Atherosclerosis.
abstract: BACKGROUND
  The renin-angiotensin system (RAS) plays an important role in atherosclerosis. Acting via the angiotensin II receptor, type 1, oxidative stress increases and contributes to endothelial dysfunction and vascular inflammation. Renin exerts effects through a renin receptor causing an increase in the efficiency of angiotensinogen cleavage and facilitates angiotensin II (Ang II) generation and action on cell surfaces. Ang II enhances proliferation and migration of vascular smooth muscle cells, indicating a direct involvement of the RAS in smooth muscle cell proliferation during neointimal formation. Aliskiren, a direct renin inhibitor, is a new oral antihypertensive drug. However, the role of the direct renin inhibitor in neointimal formation and vascular matrix metalloproteinases remains unclear.
  
  
  METHODS
  To investigate the effects of aliskiren on the expression of vascular matrix metalloproteinases, we evaluated the aortic neointimal formation of high-cholesterol-fed animals after vascular injury in vivo and the cellular function of the tumor necrosis factor-α stimulated human aortic smooth muscle cells in vitro. Thereafter, we evaluated vascular expression (by western blot), activity (by gelatin zymography) and molecular pathway.
  
  
  RESULTS
  In this study we demonstrated that aliskiren reduced neointimal hyperplasia in hypercholesterolemic rabbits after vascular injury and the expression of matrix metalloproteinases in the neointima. Aliskiren also inhibited the expression and activities of matrix metalloproteinases on tumor necrosis factor-α (TNF-α)-stimulated human aortic smooth muscle cells via the mitogen-activated protein kinase pathway.
  
  
  CONCLUSIONS
  The present study showed that aliskiren inhibited the expression of vascular matrix metalloproteinases. With these results, we have better clarified the potential role of renin inhibitors in human atherosclerosis.
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital; ; Cardiovascular Research Center.
authors.forename: Tao-Cheng
authors.initials: TC
authors.lastname: Wu
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery; ; Cardiovascular Research Center.
authors.forename: Chiu-Yang
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Cardiovascular Research Center; ; Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Cardiovascular Research Center; ; Institute of Pharmacology, National Yang-Ming University; ; Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
keywords: Matrix metalloproteinases; Neointimal hyperplasia; Renin inhibitor