Regulatory pathways governing murine coronary vessel formation are dysregulated in the injured adult heart

Sophie Payne, Mala Gunadasa-Rohling, Alice Neal, Andia N. Redpath, Jyoti Patel, Kira M. Chouliaras, Indrika Ratnayaka, Nicola Smart () and Sarah De Val ()
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Sophie Payne: University of Oxford
Mala Gunadasa-Rohling: University of Oxford
Alice Neal: University of Oxford
Andia N. Redpath: University of Oxford
Jyoti Patel: University of Oxford, John Radcliffe Hospital
Kira M. Chouliaras: University of Oxford
Indrika Ratnayaka: University of Oxford
Nicola Smart: University of Oxford
Sarah De Val: University of Oxford

Nature Communications, 2019, vol. 10, issue 1, 1-19

Abstract: Abstract The survival of ischaemic cardiomyocytes after myocardial infarction (MI) depends on the formation of new blood vessels. However, endogenous neovascularization is inefficient and the regulatory pathways directing coronary vessel growth are not well understood. Here we describe three independent regulatory pathways active in coronary vessels during development through analysis of the expression patterns of differentially regulated endothelial enhancers in the heart. The angiogenic VEGFA-MEF2 regulatory pathway is predominantly active in endocardial-derived vessels, whilst SOXF/RBPJ and BMP-SMAD pathways are seen in sinus venosus-derived arterial and venous coronaries, respectively. Although all developmental pathways contribute to post-MI vessel growth in the neonate, none are active during neovascularization after MI in adult hearts. This was particularly notable for the angiogenic VEGFA-MEF2 pathway, otherwise active in adult hearts and during neoangiogenesis in other adult settings. Our results therefore demonstrate a fundamental divergence between the regulation of coronary vessel growth in healthy and ischemic adult hearts.

Date: 2019
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DOI: 10.1038/s41467-019-10710-2

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