Document Detail

Oscillating pressure treatment upregulates connexin43 expression in skeletal myoblasts and enhances therapeutic efficacy for myocardial infarction.
MedLine Citation:
PMID:  19650969     Owner:  NLM     Status:  MEDLINE    
Transplantation of autologous skeletal myoblasts (SMBs) is a potential therapeutic approach for myocardial infarction. However, their clinical efficacy and safety is still controversial. Electrical coupling through gap junction between SMBs and host myocardium is essential for synchronized contraction and electrical stability. Here, we investigated the effect of heart beat-simulating environment, oscillating pressure, on the expression of connexin43 in two types of SMBs from rat and mouse. We found that connexin43 is markedly decreased under ischemia-mimicking conditions such as serum starvation and hypoxia (1% O(2)) in rat primary cultured SMBs and mouse C2C12 SMB cell line. Interestingly, the decrease of connexin43 expression under serum starvation was attenuated by oscillating pressure. Oscillating pressure treatment increased the expression of connexin43 twofold through AP-1 stimulation, which was blocked by PD98059, ERK inhibitor. In coculture of cardiomyocytes and C2C12, pressure-treated C2C12 and cardiomyocytes were able to form functional gap junction, which was demonstrated by both calcein-AM dye transfer assay and measurement of simultaneous contraction. In rat myocardial infarction model, transplantation of SMBs pretreated with oscillating pressure resulted in lesser ventricular dilatation and better systolic function than transplantation of untreated SMBs and control group. These results suggested that application of oscillating pressure on SMBs before transplantation may be useful to promote therapeutic efficacy for myocardial infarction by enhancing gap junction formation between transplanted and host cells.
Sae-Won Lee; Hyun-Jae Kang; Ji-Young Lee; Seock-Won Youn; Joo-Yun Won; Ji-Hyun Kim; Hyun-Chae Lee; Eun Ju Lee; Se-il Oh; Byung-Hee Oh; Young-Bae Park; Hyo-Soo Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-22
Journal Detail:
Title:  Cell transplantation     Volume:  18     ISSN:  1555-3892     ISO Abbreviation:  Cell Transplant     Publication Date:  2009  
Date Detail:
Created Date:  2010-01-27     Completed Date:  2010-04-13     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9208854     Medline TA:  Cell Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1123-35     Citation Subset:  IM    
National Research Laboratory for Cardiovascular Stem Cells and IRICT, Seoul National University Hospital, Seoul, Korea; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.
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MeSH Terms
Cell Hypoxia
Cells, Cultured
Connexin 43 / metabolism*
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors,  metabolism
Flavonoids / pharmacology
Gap Junctions / physiology
Myoblasts, Skeletal / cytology,  metabolism,  transplantation*
Myocardial Infarction / physiopathology,  therapy*
Myocardium / metabolism,  pathology
Transcription Factor AP-1 / metabolism
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Connexin 43; 0/Flavonoids; 0/Transcription Factor AP-1; EC Signal-Regulated MAP Kinases

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