摘要
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 shortening （（13.9±2.8）% vs. （18.3±2.3）%, P 〈0.05） and old-sham group, P 〈0.05）, reduced left ventricular fractiona 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.
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 shortening （（13.9±2.8）% vs. （18.3±2.3）%, P 〈0.05） and old-sham group, P 〈0.05）, reduced left ventricular fractiona 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.
基金
This study was supported by a grant from the National Natural Science Foundation of China （No. 30770865 and No. 30670849）.
