Document Detail


Protease-activated receptors and myocardial infarction.
MedLine Citation:
PMID:  21438116     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Protease-activated receptors (PARs) are widely expressed within the heart. They are activated by a myriad of proteases, including coagulation proteases. In vitro studies showed that activation of PAR-1 and PAR-2 on cardiomyocytes induced hypertrophy. In addition, PAR-1 stimulation on cardiac fibroblasts induced proliferation. Genetic and pharmacologic approaches have been used to investigate the role of the different PARs in cardiac ischemia/reperfusion (I/R) injury. In mice and rats, PAR-1 is reported to play a role in inflammation, infarct size, and remodeling after cardiac I/R injury. However, there are notable differences between the effect of a deficiency in PAR-1 and inhibition of PAR-1. For instance, inhibition of PAR-1 reduced infarct size whereas there was no effect of a deficiency of PAR-1. These differences maybe due to off-target effects of the inhibitor or PAR-4 compensation of PAR-1 deficiency. Similarly, a deficiency of PAR-2 was associated with reduced cardiac inflammation and improved heart function after I/R injury, whereas pharmacologic activation of PAR-2 was found to be protective due to increased vasodilatation. These differences maybe due to different signaling responses induced by an endogenous protease versus an exogenous agonist peptide. Surprisingly, PAR-4 deficiency resulted in increased cardiac injury and increased mortality after I/R injury. In contrast, a pharmacological study indicated that inhibition of PAR-4 was cardioprotective. It is possible that the major cellular target of the PAR-4 inhibitor is platelets, which have been shown to contribute to inflammation in the injured heart, whereas PAR-4 signaling in cardiomyocytes may be protective. These discrepant results between genetic and pharmacological approaches indicate that further studies are needed to determine the role of different PARs in the injured heart.
Authors:
Silvio Antoniak; Rafal Pawlinski; Nigel Mackman
Related Documents :
21224256 - Loss of cited2 causes congenital heart disease by perturbing left-right patterning of t...
17702356 - Non-myxomatous flail mitral valve: clinical and echocardiographic characteristics and l...
21327916 - Novel therapy for myocardial infarction: can hgf/met be beneficial?
3049286 - Understanding mitral valve prolapse (mvp).
1941986 - Technology in interventional cardiology: percutaneous transluminal coronary angioplasty.
22446876 - Improvement of myocardial lipid accumulation and prevention of pgc-1α induction by fen...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2011-03-24
Journal Detail:
Title:  IUBMB life     Volume:  63     ISSN:  1521-6551     ISO Abbreviation:  IUBMB Life     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-23     Completed Date:  2011-10-11     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  100888706     Medline TA:  IUBMB Life     Country:  England    
Other Details:
Languages:  eng     Pagination:  383-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley Periodicals, Inc.
Affiliation:
Department of Medicine, Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Humans
Myocardial Infarction / pathology,  physiopathology*
Myocardium / metabolism
Protein Isoforms / metabolism*
Receptors, Proteinase-Activated / metabolism*
Thromboplastin / metabolism
Grant Support
ID/Acronym/Agency:
HL084087/HL/NHLBI NIH HHS; R01 HL084087-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Protein Isoforms; 0/Receptors, Proteinase-Activated; 9035-58-9/Thromboplastin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Osteo-renal regulation of systemic phosphate metabolism.
Next Document:  Regulation of protease-activated receptor signaling by post-translational modifications.