From the Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY.
Arterioscler Thromb Vasc Biol. 2018 May;38(5):986-993. doi: 10.1161/ATVBAHA.117.310661. Epub 2018 Mar 29.
CypA (cyclophilin A) is a ubiquitous and highly conserved protein with peptidyl prolyl isomerase activity. Because of its highly abundant level in the cytoplasm, most studies have focused on the roles of CypA as an intracellular protein. However, emerging evidence suggests an important role for extracellular CypA in the pathogenesis of several diseases through receptor (CD147 or other)-mediated autocrine and paracrine signaling pathways. In this review, we will discuss the shared and unique pathological roles of extracellular and intracellular CypA in human cardiovascular diseases. In addition, the evolving role of post-translational modifications of CypA in the pathogenesis of disease is discussed. Finally, recent studies with drugs specific for extracellular CypA show its importance in disease pathogenesis in several animal models and make extracellular CypA a new therapeutic target.
CypA（亲环素 A）是一种普遍存在且高度保守的蛋白，具有肽基脯氨酰顺反异构酶活性。由于其在细胞质中含量极高，大多数研究都集中在 CypA 作为细胞内蛋白的作用上。然而，新出现的证据表明，细胞外 CypA 通过受体（CD147 或其他）介导的自分泌和旁分泌信号通路在几种疾病的发病机制中起着重要作用。在这篇综述中，我们将讨论细胞外和细胞内 CypA 在人类心血管疾病中的共同和独特的病理作用。此外，还讨论了 CypA 的翻译后修饰在疾病发病机制中的作用。最后，针对细胞外 CypA 的特定药物的最新研究表明，它在几种动物模型的疾病发病机制中具有重要意义，使细胞外 CypA 成为一个新的治疗靶点。
