title: Direct renin inhibitor, aliskiren, attenuates the progression of non-alcoholic steatohepatitis in the rat model.
abstract: OBJECTIVE
  Renin is a rate-limiting enzyme of the renin-angiotensin system (RAS), and several reports have shown that renin plays an important role in several pathological processes. Although RAS is known to play a pivotal role in the progression of non-alcoholic steatohepatitis (NASH), the role of renin is still obscure. The aim of the current study was to examine the effect of the clinically used direct renin inhibitor (DRI), aliskiren, on the progression of NASH in a rat model.
  
  
  METHODS
  The effects of DRI on the choline-deficient L-amino acid-defined (CDAA) diet-induced rat NASH model was examined in conjunction with the activated hepatic stellate cells (Ac-HSC) and neovascularization, both of which are known to play important roles in liver fibrosis development and hepatocarcinogenesis, respectively.
  
  
  RESULTS
  DRI exerted a marked inhibitory effect against liver fibrosis development and glutathione-S-transferase placental form (GST-P) positive preneoplastic lesions along with suppression of the Ac-HSC and neovascularization in a dose-dependent manner. DRI also inhibited the hepatic expressions of transforming growth factor-beta 1 (TGF-beta 1), angiotensin-II (AT-II) and vascular endothelial growth factor (VEGF). These results indicated that renin played a pivotal role in the liver fibrosis development and hepatocarcinogenesis of NASH.
  
  
  CONCLUSIONS
  Because DRI is already widely used in the clinical practice with safety, this drug may represent a potential new strategy against the progression of NASH in the future.
authors: Third Department of Internal Medicine, Nara Medical University, Nara, Japan.
authors: Yosuke
authors: Y
authors: Aihara
authors: Hitoshi
authors: H
authors: Yoshiji
authors: Ryuichi
authors: R
authors: Noguchi
authors: Kosuke
authors: K
authors: Kaji
authors: Tadashi
authors: T
authors: Namisaki
authors: Yusaku
authors: Y
authors: Shirai
authors: Akitoshi
authors: A
authors: Douhara
authors: Kei
authors: K
authors: Moriya
authors: Hideto
authors: H
authors: Kawaratani
authors: Hiroshi
authors: H
authors: Fukui
keywords: angiotensin-II; hepatocarcinogenesis; liver fibrosis; non-alcoholic steatohepatitis; renin