The Cardioprotective Signaling Activity of Activated Protein C in Heart Failure and Ischemic Heart Diseases
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. T...
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doaj-97fe71b989874b10b5017bf4a26177c72020-11-24T21:44:25ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-04-01207176210.3390/ijms20071762ijms20071762The Cardioprotective Signaling Activity of Activated Protein C in Heart Failure and Ischemic Heart DiseasesDi Ren0Hemant Giri1Ji Li2Alireza R. Rezaie3Department of Physiology and Biophysics, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, MS 39216, USACardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USADepartment of Physiology and Biophysics, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, MS 39216, USACardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USAActivated 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.https://www.mdpi.com/1422-0067/20/7/1762activated protein Cendothelial protein C receptorheart failureischemic heart diseasecardioprotection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Di Ren Hemant Giri Ji Li Alireza R. Rezaie |
spellingShingle |
Di Ren Hemant Giri Ji Li Alireza R. Rezaie The Cardioprotective Signaling Activity of Activated Protein C in Heart Failure and Ischemic Heart Diseases International Journal of Molecular Sciences activated protein C endothelial protein C receptor heart failure ischemic heart disease cardioprotection |
author_facet |
Di Ren Hemant Giri Ji Li Alireza R. Rezaie |
author_sort |
Di Ren |
title |
The Cardioprotective Signaling Activity of Activated Protein C in Heart Failure and Ischemic Heart Diseases |
title_short |
The Cardioprotective Signaling Activity of Activated Protein C in Heart Failure and Ischemic Heart Diseases |
title_full |
The Cardioprotective Signaling Activity of Activated Protein C in Heart Failure and Ischemic Heart Diseases |
title_fullStr |
The Cardioprotective Signaling Activity of Activated Protein C in Heart Failure and Ischemic Heart Diseases |
title_full_unstemmed |
The Cardioprotective Signaling Activity of Activated Protein C in Heart Failure and Ischemic Heart Diseases |
title_sort |
cardioprotective signaling activity of activated protein c in heart failure and ischemic heart diseases |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-04-01 |
description |
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. |
topic |
activated protein C endothelial protein C receptor heart failure ischemic heart disease cardioprotection |
url |
https://www.mdpi.com/1422-0067/20/7/1762 |
work_keys_str_mv |
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