Document Detail

VEGF-C and aortic cardiomyocytes guide coronary artery stem development.
MedLine Citation:
PMID:  25271623     Owner:  NLM     Status:  Publisher    
Coronary arteries (CAs) stem from the aorta at 2 highly stereotyped locations, deviations from which can cause myocardial ischemia and death. CA stems form during embryogenesis when peritruncal blood vessels encircle the cardiac outflow tract and invade the aorta, but the underlying patterning mechanisms are poorly understood. Here, using murine models, we demonstrated that VEGF-C-deficient hearts have severely hypoplastic peritruncal vessels, resulting in delayed and abnormally positioned CA stems. We observed that VEGF-C is widely expressed in the outflow tract, while cardiomyocytes develop specifically within the aorta at stem sites where they surround maturing CAs in both mouse and human hearts. Mice heterozygous for islet 1 (Isl1) exhibited decreased aortic cardiomyocytes and abnormally low CA stems. In hearts with outflow tract rotation defects, misplaced stems were associated with shifted aortic cardiomyocytes, and myocardium induced ectopic connections with the pulmonary artery in culture. These data support a model in which CA stem development first requires VEGF-C to stimulate vessel growth around the outflow tract. Then, aortic cardiomyocytes facilitate interactions between peritruncal vessels and the aorta. Derangement of either step can lead to mispatterned CA stems. Studying this niche for cardiomyocyte development, and its relationship with CAs, has the potential to identify methods for stimulating vascular regrowth as a treatment for cardiovascular disease.
Heidi I Chen; Aruna Poduri; Harri Numi; Riikka Kivela; Pipsa Saharinen; Andrew S McKay; Brian Raftrey; Jared Churko; Xueying Tian; Bin Zhou; Joseph C Wu; Kari Alitalo; Kristy Red-Horse
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-1
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  -     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-1     Completed Date:  -     Revised Date:  2014-10-2    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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