title: ADAMTS-1 expression in rat myocardium after ischemic preconditioning: age-associated differences.
abstract: BACKGROUND
  It has been found that cardiac protection afforded by ischemic preconditioning (IPC) is significantly reduced in the senescent myocardium. ADAMTS-1 (a disintesrin and metalloprotease with thrombospondin type 1 motifs) has been shown to inhibit angiogenesis in a variety of in vitro and in vivo assays. The aim of this study was to investigate the age-associated differences in ADAMTS-1 protein expression in rat myocardium after ischemic preconditioning.
  
  
  METHODS
  Sixty-four young (4 months) and old (24 months) male Sprague-Dawley rats were randomly assigned to an IPC group (40 rats) or a sham group (rats). A model of delayed IPC was induced and rats were sacrificed and myocardial samples were harvested from the ischemic-reperfused region for immunohistochemical detection of ADAMTS-1 at serial time points after IPC. A model of myocardial infarction was produced by ligation of the left anterior descending coronary artery in additional sets of young and old rats after sham or IPC procedures, then age-associated myocardial infarction survival after IPC was calculated.
  
  
  RESULTS
  ADAMTS-1 expression increased significantly in old rats compared to young rats (P < 0.05). The mean densities of ADAMTS-1 protein at 0, 6, 12, and 24 hours in young-IPC group after IPC were 0.05 ± 0.01, 0.13 ± 0.03, 0.16 ± 0.04, and 0.12 ± 0.03 vs. 0.07 ± 0.03, 0.20 ± 0.03, 0.24 ± 0.05, and 0.21 ± 0.04 in old-IPC group. IPC resulted in diminished survival rates (5/35 vs. 6/14, old-IPC group vs. old-sham group, P < 0.05), reduced left ventricular fractional shortening ((13.9 ± 2.8)% vs. (18.3 ± 2.3)%, P < 0.05) and increased the myocardial infarction size ((37.9 ± 3.2)% vs. (32.8 ± 5.1)%, P < 0.05) in the older rats.
  
  
  CONCLUSIONS
  Cardioprotection with IPC is attenuated in the older heart. ADAMTS-1 expression induced by IPC is greater in old rats. Over-expression of anti-angiogenic factors might be a potential mechanism behind reduced protection after IPC associated with aging.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Cong-Xin
authors.initials: CX
authors.lastname: Huang
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Zhou
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Cheng
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Wu
authors.forename: Wen-Qiang
authors.initials: WQ
authors.lastname: Liao
authors.forename: Jian-Yan
authors.initials: JY
authors.lastname: Wen
authors.forename: Yuan-Nan
authors.initials: YN
authors.lastname: Ke
authors.forename: Jin-Gang
authors.initials: JG
authors.lastname: Zheng
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D000375:Aging / Q000378:metabolism / Q000502:physiology; D000818:Animals; D007150:Immunohistochemistry; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C486324:Adamts1 protein, rat