HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The Cardioprotective Signaling Activity of Activated Protein C in Heart Failure and Ischemic Heart Diseases.

Abstract
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.
AuthorsDi Ren, Hemant Giri, Ji Li, Alireza R Rezaie
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 7 (Apr 10 2019) ISSN: 1422-0067 [Electronic] Switzerland
PMID30974752 (Publication Type: Journal Article, Review)
Chemical References
  • Anticoagulants
  • Endothelial Protein C Receptor
  • PROCR protein, human
  • Protein C
  • Receptor, PAR-1
  • Phosphatidylinositol 3-Kinases
  • Mechanistic Target of Rapamycin Complex 1
Topics
  • Animals
  • Anticoagulants (metabolism)
  • Blood Coagulation
  • Endothelial Protein C Receptor (metabolism)
  • Heart Failure (metabolism, pathology)
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 (metabolism)
  • Myocardial Ischemia (metabolism, pathology)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Protein C (metabolism)
  • Receptor, PAR-1 (metabolism)
  • Signal Transduction

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: