ADAMTS-1 expression in rat myocardium after ischemic preconditioning: age-associated differences

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.