The a disintegrin-like and metalloproteinase with thrombospondin motif (ADAMTS) family comprises 19 proteases that regulate the structure and function of extracellular proteins in the extracellular matrix and blood. The best characterized cardiovascular role is that of ADAMTS-13 in blood. Moderately low ADAMTS-13 levels increase the risk of ischeamic stroke and very low levels (less than 10%) can cause thrombotic thrombocytopenic purpura (TTP). Recombinant ADAMTS-13 is currently in clinical trials for treatment of TTP. Recently, new cardiovascular roles for ADAMTS proteases have been discovered. Several ADAMTS family members are important in the development of blood vessels and the heart, especially the valves. A number of studies have also investigated the potential role of ADAMTS-1, -4 and -5 in cardiovascular disease. They cleave proteoglycans such as versican, which represent major structural components of the arteries. ADAMTS-7 and -8 are attracting considerable interest owing to their implication in atherosclerosis and pulmonary arterial hypertension, respectively. Mutations in the ADAMTS19 gene cause progressive heart valve disease and missense variants in ADAMTS6 are associated with cardiac conduction. In this review, we discuss in detail the evidence for these and other cardiovascular roles of ADAMTS family members, their proteolytic substrates and the potential molecular mechanisms involved.

具有血小板反应蛋白基序的解整合素样金属蛋白酶 (ADAMTS) 家族包含 19 种蛋白酶，可调节细胞外基质和血液中细胞外蛋白的结构和功能。最具代表性的心血管作用是血液中的 ADAMTS-13。中度低的 ADAMTS-13 水平会增加缺血性中风的风险，非常低的水平（低于 10%）会导致血栓性血小板减少性紫癜 (TTP)。重组 ADAMTS-13 目前正在临床试验中用于治疗 TTP。最近，发现了 ADAMTS 蛋白酶的新心血管作用。几个 ADAMTS 家族成员在血管和心脏的发育中很重要，尤其是瓣膜。许多研究还调查了 ADAMTS-1、-4 和 -5 在心血管疾病中的潜在作用。它们切割蛋白多糖，如多功能蛋白聚糖，它代表了动脉的主要结构成分。ADAMTS-7 和 -8 由于它们分别对动脉粥样硬化和肺动脉高压的影响而引起了相当大的兴趣。中的突变ADAMTS19基因导致进行性心脏瓣膜疾病，ADAMTS6中的错义变异与心脏传导有关。在这篇综述中，我们详细讨论了 ADAMTS 家族成员的这些和其他心血管作用的证据、它们的蛋白水解底物和所涉及的潜在分子机制。