title: [Association between lysosomal cysteine protease cathepsin's activation and left ventricular function and remodeling in hypertensive heart failure rats].
abstract: OBJECTIVE
  To observe myocardial cathepsin (Cat) S expression and activity in hypertensive heart failure rats.
  
  
  METHODS
  The expression and activity of Cat S were determined in the left ventricular (LV) myocardium (LVM) of Dahl salt-sensitive rats fed either a high-salt (HS, 8%) or low-salt (LS, 0, 3%, controls) diet starting at age 7 weeks for 12 weeks (hypertrophy model, H-LVH) or 19 weeks (heart failure model, H-HF). Age-matched rats served as controls and human normal, hypertensive and heart failure myocardial specimen were also examined for changes on the expression and activity of Cat S.
  
  
  RESULTS
  Reverse transcription and real-time polymerase chain reaction analysis revealed significantly upregulated Cat S mRNA in rats with H-HF than in rats with H-LVH or in control rats and Cat S mRNA expression is negatively correlated with LVEF (r = -0.88, P < 0.05). In situ and immunohistochemistry examinations showed that Cat S was localized predominantly in cardiac myocytes (CMCs) and coronary vascular smooth muscle cells (SMC). Elastic lamina fragmentations and Cat S-dependent elastolytic activity were significantly increased in H-HF-rats. The expression of interleukin-1 beta was also increased in the LVM of H-HF rats, and this cytokine was found to increase the Cat S protein expression in culture neonatal CMCs. Similar results were revealed in human myocardial specimens.
  
  
  CONCLUSIONS
  Elastolytic Cat S might play an important role in the pathogenesis of myocardial remodeling and heart failure and Cat S might serve as a novel therapeutic target in preventing or reversing hypertension induced LV remodeling and heart failure.
authors.affiliation: Department of Cardiovascular Research Medicine, Nagoya University School of Medicine, Aichiken, Nagoya 466-8550, Japan. xianwu@med.nagoya-u.ac.jp
authors.forename: Xian-Wu
authors.initials: XW
authors.lastname: Cheng
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Song
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Xiao-Zhi
authors.initials: XZ
authors.lastname: Qin
authors.forename: Li-Ke
authors.initials: LK
authors.lastname: Guan
authors.forename: Hai
authors.initials: H
authors.lastname: Jin
authors.forename: Kenji
authors.initials: K
authors.lastname: Okumura
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002403:Cathepsins / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006333:Heart Failure / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D020303:Rats, Inbred Dahl; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D002403:Cathepsins; C028217:cathepsin S