Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Experiment Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, University of Alberta, Alberta, Canada.
Atherosclerosis. 2018 Nov;278:250-258. doi: 10.1016/j.atherosclerosis.2018.10.004. Epub 2018 Oct 9.
Pregnancy-associated plasma protein-A (PAPP-A), a member of the metzincin metalloproteinase superfamily, can enhance local insulin-like growth factor (IGF) bioavailability through proteolytic cleavage of three IGF binding proteins. In patients with coronary atherosclerosis disease (CAD), elevated PAPP-A levels are significantly associated with a higher risk of cardiovascular events. Accumulating evidence indicates that this protease exerts a proatherogenic effect by altering a variety of pathological processes involved in atherosclerosis, including lipid accumulation, vascular inflammation, endothelial dysfunction, vascular smooth muscle cell proliferation and migration, plaque stability, and thrombus formation. Moreover, blockade of its proteolytic activity by stanniocalcin or microRNAs is protective against atherosclerosis development. In this review, we summarized the latest advances regarding the roles of PAPP-A in the pathogenesis of atherosclerosis with an emphasis on its diagnostic and prognostic values in CAD.
妊娠相关血浆蛋白 A（PAPP-A）是金属蛋白酶超家族的成员，可通过蛋白水解切割三种胰岛素样生长因子（IGF）结合蛋白来增强局部 IGF 的生物利用度。在患有冠状动脉粥样硬化疾病（CAD）的患者中，升高的 PAPP-A 水平与心血管事件的风险增加显著相关。越来越多的证据表明，这种蛋白酶通过改变参与动脉粥样硬化的多种病理过程发挥促动脉粥样硬化作用，包括脂质积累、血管炎症、内皮功能障碍、血管平滑肌细胞增殖和迁移、斑块稳定性和血栓形成。此外，通过 Stanniocalcin 或 microRNAs 阻断其蛋白水解活性可防止动脉粥样硬化的发展。在这篇综述中，我们总结了 PAPP-A 在动脉粥样硬化发病机制中的最新进展，重点介绍了其在 CAD 中的诊断和预后价值。
