Department of Physiology, Cardiovascular Research Center, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada (T.K., Z.K.).
Cardiovascular Research Center and Department of Cardiovascular Science, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.O., S.E.).
Hypertension. 2022 Jul;79(7):1327-1338. doi: 10.1161/HYPERTENSIONAHA.122.17963. Epub 2022 May 11.
Aortic aneurysm is a complex pathology that can be lethal if not detected in time. Although several molecular mechanisms and pathways have been identified to be involved in aortic aneurysm development and growth, the current lack of an effective pharmacological treatment highlights the need for a more thorough understanding of the factors that regulate the remodeling of the aortic wall in response to triggers that lead to aneurysm formation. This task is further complicated by the regional heterogeneity of the aorta and that thoracic and abdominal aortic aneurysm are distinct pathologies with different risk factors and distinct course of progression. ADAMs (a disintegrin and metalloproteinases) and ADAMTS (ADAMs with a thrombospondin motif) are proteinases that share similarities with other proteinases but possess unique and diverse properties that place them in a category of their own. In this review, we discuss what is known on how ADAMs and ADAMTSs are altered in abdominal aortic aneurysm and thoracic aortic aneurysm in patients, in different animal models, and their role in regulating the function of different vascular and inflammatory cell types. A full understanding of the role of ADAMs and ADAMTSs in aortic aneurysm will help reveal a more complete understanding of the underlying mechanism driving aneurysm formation, which will help towards developing an effective treatment in preventing or limiting the growth of aortic aneurysm.
腹主动脉瘤是一种复杂的病理学疾病，如果不能及时发现，可能会致命。虽然已经确定了几个分子机制和途径参与了腹主动脉瘤的发展和生长，但目前缺乏有效的药物治疗方法，这突出表明需要更深入地了解调节主动脉壁重塑的因素，以应对导致动脉瘤形成的触发因素。这项任务更加复杂，因为主动脉具有区域异质性，而且胸主动脉瘤和腹主动脉瘤是两种不同的病理学疾病，具有不同的危险因素和不同的进展过程。ADAMs（解整合素和金属蛋白酶）和 ADAMTS（具有血小板反应蛋白基序的 ADAMs）是蛋白酶，它们与其他蛋白酶具有相似之处，但具有独特和多样化的特性，使它们自成一类。在这篇综述中，我们讨论了在患者、不同动物模型中腹主动脉瘤和胸主动脉瘤中 ADAMs 和 ADAMTS 是如何改变的，以及它们在调节不同血管和炎症细胞类型功能中的作用。全面了解 ADAMs 和 ADAMTS 在主动脉瘤中的作用将有助于揭示驱动动脉瘤形成的潜在机制的更完整理解，这将有助于开发预防或限制主动脉瘤生长的有效治疗方法。
