期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/ijms20071762
关键词
activated protein C; endothelial protein C receptor; heart failure; ischemic heart disease; cardioprotection
资金
- National Heart, Lung, and Blood Institute of the National Institutes of Health [HL101917, HL062565]
- National Heart, Lung, and Blood Institute [P01HL051971]
- National Institute on Aging [AG049835]
- National Institute of General Medicine [GM124108, P20GM104357]
Activated protein C (APC) is a vitamin-K dependent plasma serine protease, which functions as a natural anticoagulant to downregulate thrombin generation in the clotting cascade. APC also modulates cellular homeostasis by exhibiting potent cytoprotective and anti-inflammatory signaling activities. The beneficial cytoprotective effects of APC have been extensively studied and confirmed in a number of preclinical disease and injury models including sepsis, type-1 diabetes and various ischemia/reperfusion diseases. It is now well-known that APC modulates downstream cell signaling networks and transcriptome profiles when it binds to the endothelial protein C receptor (EPCR) to activate protease-activated receptor 1 (PAR1) on various cell types. However, despite much progress, details of the downstream signaling mechanism of APC and its crosstalk with other signaling networks are far from being fully understood. In this review, we focus on the cardioprotective properties of APC in ischemic heart disease and heart failure with a special emphasis on recent discoveries related to the modulatory effect of APC on AMP-activated protein kinase (AMPK), PI3K/AKT, and mTORC1 signaling pathways. The cytoprotective properties of APC might provide a novel strategy for future therapies in cardiac diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据