Document Detail


Cardiac intercellular communication: are myocytes and fibroblasts fair-weather friends?
MedLine Citation:
PMID:  23015462     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cardiac fibroblast (CF) has historically been thought of as a quiescent cell of the heart, passively maintaining the extracellular environment for the cardiomyocytes (CM), the functional cardiac cell type. The increasingly appreciated role of the CF, however, extends well beyond matrix production, governing many aspects of cardiac function including cardiac electrophysiology and contractility. Importantly, its contributions to cardiac pathophysiology and pathologic remodeling have created a shift in the field's focus from the CM to the CF as a therapeutic target in the treatment of cardiac diseases. In response to cardiac injury, the CF undergoes a pathologic phenotypic transition into a myofibroblast, characterized by contractile smooth muscle proteins and upregulation of collagens, matrix proteins, and adhesion molecules. Further, the myofibroblast upregulates expression and secretion of a variety of pro-inflammatory, profibrotic mediators, including cytokines, chemokines, and growth factors. These mediators act in both an autocrine fashion to further activate CFs, as well as in a paracrine manner on both CMs and circulating inflammatory cells to induce myocyte dysfunction and chronic inflammation, respectively. Together, cell-specific cytokine-induced effects exacerbate pathologic remodeling and progression to HF. A better understanding of this dynamic intercellular communication will lead to novel targets for the attenuation of cardiac remodeling. Current strategies aimed at targeting cytokines have been largely unsuccessful in clinical trials, lending insights into ways that such intercellular cross talk can be more effectively attenuated. This review will summarize the current knowledge regarding CF functions in the heart and will discuss the regulation and signaling behind CF-mediated cytokine production and function. We will then highlight clinical trials that have exploited cytokine cross talk in the treatment of heart failure and provide novel strategies currently under investigation that may more effectively target pathologic CF-CM communication for the treatment of cardiac disease. This review explores novel mechanisms to directly attenuate heart failure progression through inhibition of signaling downstream of pro-inflammatory cytokines that are elevated after cardiac injury.
Authors:
Melissa L Martin; Burns C Blaxall
Publication Detail:
Type:  Journal Article; Review     Date:  2012-09-27
Journal Detail:
Title:  Journal of cardiovascular translational research     Volume:  5     ISSN:  1937-5395     ISO Abbreviation:  J Cardiovasc Transl Res     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-11     Completed Date:  2013-05-21     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  101468585     Medline TA:  J Cardiovasc Transl Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  768-82     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents / therapeutic use
Biological Markers / metabolism
Cardiovascular Agents / therapeutic use
Cell Communication* / drug effects
Cytokines / antagonists & inhibitors,  metabolism
Fibroblasts / drug effects,  metabolism*,  pathology
Heart Failure / drug therapy,  metabolism*,  pathology,  physiopathology
Humans
Inflammation Mediators / antagonists & inhibitors,  metabolism
Myocytes, Cardiac / drug effects,  metabolism*,  pathology
Myofibroblasts / metabolism,  pathology
Phenotype
Signal Transduction
Grant Support
ID/Acronym/Agency:
R01 HL089885/HL/NHLBI NIH HHS; R01 HL091475/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Biological Markers; 0/Cardiovascular Agents; 0/Cytokines; 0/Inflammation Mediators
Comments/Corrections

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