Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine.
Circ J. 2017 Oct 25;81(11):1557-1563. doi: 10.1253/circj.CJ-17-1029. Epub 2017 Oct 6.
Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells, inflammatory cells, activated platelets, and cardiac fibroblasts in response to oxidative stress. Excessive and continuous activation of the RhoA/Rho-kinase system promotes the secretion of CyPA, resulting in the development of multiple cardiovascular diseases. Basigin (Bsg), a transmembrane glycoprotein that activates matrix metalloproteinases, is an extracellular receptor for CyPA that promotes cell proliferation and inflammation. Thus, the CyPA/Bsg system is potentially a novel therapeutic target for cardiovascular diseases. Importantly, plasma CyPA levels are increased in patients with coronary artery disease, abdominal aortic aneurysms, pulmonary hypertension, and heart failure. Moreover, plasma CyPA levels can predict all-cause death in patients with coronary artery disease and pulmonary hypertension. Additionally, plasma soluble Bsg levels are increased and predict all-cause death in patients with heart failure, suggesting that CyPA and Bsg are novel biomarkers for cardiovascular diseases. To discover further novel molecules targeting the CyPA/Bsg system, high-throughput screening of compounds found molecules that ameliorate the development of cardiovascular diseases. In addition to CyPA and Bsg, novel therapeutic targets and their inhibitors for patients with pulmonary arterial hypertension have been recently screened and identified. Ultimately, the final goal is to develop novel biomarkers and medications that will be useful for improving the prognosis and quality of life in patients with cardiovascular diseases.
亲环素 A（CyPA）在氧化应激的情况下从血管平滑肌细胞、炎性细胞、活化的血小板和心脏成纤维细胞中分泌。RhoA/Rho 激酶系统的过度和持续激活促进 CyPA 的分泌，导致多种心血管疾病的发生。Basigin（Bsg）是一种激活基质金属蛋白酶的跨膜糖蛋白，是 CyPA 的细胞外受体，促进细胞增殖和炎症。因此，CyPA/Bsg 系统可能是心血管疾病的一个新的治疗靶点。重要的是，冠心病、腹主动脉瘤、肺动脉高压和心力衰竭患者的血浆 CyPA 水平升高。此外，血浆 CyPA 水平可以预测冠心病和肺动脉高压患者的全因死亡。此外，心力衰竭患者的血浆可溶性 Bsg 水平升高并预测全因死亡，表明 CyPA 和 Bsg 是心血管疾病的新型生物标志物。为了发现针对 CyPA/Bsg 系统的进一步新型分子，对化合物进行了高通量筛选，发现了一些可以改善心血管疾病发展的分子。除了 CyPA 和 Bsg 之外，最近还筛选和鉴定了肺动脉高压患者的新型治疗靶点及其抑制剂。最终目标是开发新型的生物标志物和药物，以改善心血管疾病患者的预后和生活质量。
