School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Street, Nanjing 210009, China.
Jiangsu Center for Pharmacodynamics Research, Evaluation and Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Int J Mol Sci. 2018 Feb 14;19(2):573. doi: 10.3390/ijms19020573.
Cardiovascular diseases (CVDs) are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs), including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR). Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.
心血管疾病（CVDs）是目前全球范围内主要的死亡原因之一。血小板聚集是动脉血栓形成的关键细胞成分，也是 CVDs 的主要原因。蛋白酶激活受体（PARs），包括 PAR1、PAR2、PAR3 和 PAR4，属于七跨膜 G 蛋白偶联受体（GPCR）的一个亚家族。人血小板表达 PAR1 和 PAR4，它们参与信号转导过程。与 CVDs 相关联，PAR4 不仅有助于血小板激活，而且还是细胞反应的调节剂，这些反应是炎症的标志。尽管市场上有几种抗血小板药物，但它们有许多副作用限制了它们的使用。新出现的证据表明，PAR4 靶向是预防血栓形成的更安全策略，因此可能会改善整体心脏安全性。我们目前的综述总结了 PAR4 的结构特征、激活机制、在疾病病理生理学中的作用以及了解 PAR4 靶向以改善心脏保护的相关性。总之，该综述强调了 PAR4 拮抗剂的重要性及其在不同 CVDs 中的潜在应用。
