Coupled myovascular expansion directs cardiac growth and regeneration

Journal Article

ABSTRACTBackgroundHeart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mouse heart and find that they are spatiotemporally coupled.Methods and ResultsWe show that coupled myovascular expansion during cardiac growth or regeneration is dependent upon VEGF-VEGFR2 signaling, as genetic deletion of Vegfr2 from CECs or inhibition of VEGFA abrogates both CEC and CM proliferation. Repair of cryoinjury displays poor spatial coupling of CEC and CM proliferation. Boosting CEC density after cryoinjury with virus encoding Vegfa enhances regeneration. Using Mendelian randomization, we demonstrate that circulating VEGFA levels are positively linked with human myocardial mass, suggesting that Vegfa can stimulate human cardiac growth.ConclusionsOur work demonstrates the importance of coupled CEC and CM expansion and reveals a myovascular niche that may be therapeutically targeted for heart regeneration.

Full Text

Duke Authors

Cited Authors

  • DeBenedittis, P; Karpurapu, A; Henry, A; Thomas, MC; McCord, TJ; Brezitski, K; Prasad, A; Kobayashi, Y; Shah, SH; Kontos, CD; Tata, PR; Lumbers, RT; Karra, R

Published Date

  • January 21, 2021

Digital Object Identifier (DOI)

  • 10.1101/2021.01.20.425322