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Regulation of the inflammatory response in cardiac repair.
MedLine Citation:
PMID:  22223212     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Myocardial necrosis triggers an inflammatory reaction that clears the wound from dead cells and matrix debris, while activating reparative pathways necessary for scar formation. A growing body of evidence suggests that accentuation, prolongation, or expansion of the postinfarction inflammatory response results in worse remodeling and dysfunction following myocardial infarction. This review manuscript discusses the cellular effectors and endogenous molecular signals implicated in suppression and containment of the inflammatory response in the infarcted heart. Clearance of apoptotic neutrophils, recruitment of inhibitory monocyte subsets and regulatory T cells, macrophage differentiation and pericyte/endothelial interactions may play an active role in restraining postinfarction inflammation. Multiple molecular signals may be involved in suppressing the inflammatory cascade. Negative regulation of toll-like receptor signaling, downmodulation of cytokine responses, and termination of chemokine signals may be mediated through the concerted action of multiple suppressive pathways that prevent extension of injury and protect from adverse remodeling. Expression of soluble endogenous antagonists, decoy receptors, and posttranslational processing of bioactive molecules may limit cytokine and chemokine actions. Interleukin-10, members of the transforming growth factor-β family, and proresolving lipid mediators (such as lipoxins, resolvins, and protectins) may suppress proinflammatory signaling. In human patients with myocardial infarction, defective suppression, and impaired resolution of inflammation may be important mechanisms in the pathogenesis of remodeling and in progression to heart failure. Understanding of inhibitory and proresolving signals in the infarcted heart and identification of patients with uncontrolled postinfarction inflammation and defective cardiac repair is needed to design novel therapeutic strategies.
Authors:
Nikolaos G Frangogiannis
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Circulation research     Volume:  110     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  159-73     Citation Subset:  IM    
Affiliation:
Division of Cardiology, Albert Einstein College of Medicine, 1300 Morris Park Avenue Forchheimer G46B, Bronx NY 10461. nikolaos.frangogiannis@einstein.yu.edu.
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