Qin Yanwen, Cao Xu, Yang Yaoguo, Shi Guo-Ping
The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, Beijing Institute of Heart, Lung & Blood Vessel Diseases, Beijing 100029, China.
Future Cardiol. 2013 Jan;9(1):89-103. doi: 10.2217/fca.12.71.
Both cysteine protease cathepsins and matrix metalloproteinases are implicated in the pathogenesis of abdominal aortic aneurysms (AAAs) in humans and animals. Blood and aortic tissues from humans or animals with AAAs contain much higher levels of these proteases, and often lower levels of their endogenous inhibitors, than do blood and aortic tissues from healthy subjects. Protease- and protease inhibitor-deficient mice and synthetic protease inhibitors have affirmed that cysteinyl cathepsins and matrix metalloproteinases both participate directly in AAA development in several experimental model systems. Here, we summarize our current understanding of how proteases contribute to the pathogenesis of AAA, and discuss whether proteases or their inhibitors may serve as diagnostic biomarkers or potential therapeutic targets for this common human arterial disease.
半胱氨酸蛋白酶组织蛋白酶和基质金属蛋白酶均与人类和动物腹主动脉瘤(AAA)的发病机制有关。与健康受试者的血液和主动脉组织相比,患有AAA的人类或动物的血液和主动脉组织中这些蛋白酶的水平要高得多,而其内源抑制剂的水平通常较低。蛋白酶和蛋白酶抑制剂缺陷型小鼠以及合成蛋白酶抑制剂已证实,在多个实验模型系统中,半胱氨酸组织蛋白酶和基质金属蛋白酶均直接参与AAA的发展。在此,我们总结了目前对蛋白酶如何导致AAA发病机制的理解,并讨论了蛋白酶或其抑制剂是否可作为这种常见人类动脉疾病的诊断生物标志物或潜在治疗靶点。