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Complement component 3 is necessary to preserve myocardium and myocardial function in chronic myocardial infarction.
MedLine Citation:
PMID:  24806427     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Activation of the complement cascade (CC) with myocardial infarction (MI) acutely initiates immune cell infiltration, membrane attack complex formation on injured myocytes, and exacerbates myocardial injury. Recent studies implicate the CC in mobilization of stem/progenitor cells and tissue regeneration. Its role in chronic MI is unknown. Here, we consider complement component C3, in the chronic response to MI. C3 knockout (KO) mice were studied after permanent coronary artery ligation. C3 deficiency exacerbated myocardial dysfunction 28 days after MI compared to WT with further impaired systolic function and LV dilation despite similar infarct size 24 hours post-MI. Morphometric analysis 28 days post-MI showed C3 KO mice had more scar tissue with less viable myocardium within the infarct zone which correlated with decreased c-kit(pos) cardiac stem/progenitor cells (CPSC), decreased proliferating Ki67(pos) CSPCs and decreased formation of new BrdU(pos) /α-sarcomeric actin(pos) myocytes and increased apoptosis compared to WT. Decreased CSPCs and increased apoptosis were evident 7 days post-MI in C3 KO hearts. The inflammatory response with MI was attenuated in the C3 KO and was accompanied by attenuated hematopoietic, pluripotent, and cardiac stem/progenitor cell mobilization into the peripheral blood 72 hours post-MI. These results are the first to demonstrate the CC, through C3, contributes to myocardial preservation and regeneration in response to chronic MI. Responses in the C3 KO infer that C3 activation in response to MI expands the resident CSPC population, increases new myocyte formation, increases and preserves myocardium, inflammatory response, and bone marrow stem/progenitor cell mobilization to preserve myocardial function. Stem Cells 2014.
Authors:
Marcin Wysoczynski; Mitesh Solanki; Sylwia Julita Borkowska; Patrick van Hoose; Kenneth R Brittian; Sumanth D Prabhu; Mariusz Z Ratajczak; Gregg Rokosh
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-8
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  -     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-5-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 AlphaMed Press.
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