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.
含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶ADAMTSs(a disintegrin and metallo-proteinase with thrombospondin motifs)是一类新的Zn2+依赖的金属蛋白酶家族,广泛存在于哺乳动物和无脊椎动物体内。从1997年发现第一个ADAMTSs家族成员以来,迄今共有19个成员被发现,在保持凝血系统的稳态、器官生成、炎症、生育等方面有重要作用。尽管其中大部分酶的功能尚不清楚,但已有研究显示该家族成员与多种疾病密切相关。ADAMTSs与基质金属蛋白酶MMPs、解聚蛋白样金属蛋白酶ADAMs同属金属蛋白酶家族,但在结构组成、组织细胞分布、底物作用的特异性、酶活性的调节等方面有明显差别。本文综述了其在结构功能及与疾病关系的研究进展。
血管重塑是动脉粥样硬化和血管再狭窄发病中的一个重要的病理生理学过程。越来越多的证据表明,具有降解细胞外基质能力的酶在血管重塑中发挥着重要的作用。含I型血小板反应蛋白的解聚素和金属蛋白酶(a disintegrin and metalloproteinase with thrombospondin motifs,ADAMTS)家族是一类最近被克隆的金属蛋白酶家族,该家族成员同样具备降解细胞外基质的能力。ADAMTS家族由19个家族成员组成,参与了一系列的正常生理学功能,如发育、血管新生和凝血等。而ADAMTS家族成员的异常表达通常会引发各种疾病,如关节炎、肿瘤、凝血功能障碍性紫癜。本文从ADAMTS家族第七个成员——ADAMTS-7的结构、组织分布、调控、尤其是通过其底物软骨寡聚基质蛋白(cartilage oligomeric matrix protein,COMP)精细调控血管稳态几个方面综述了其在血管重塑中作用的最新研究进展。
