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Coupled myovascular expansion directs cardiac growth and regeneration

DeBenedittis, Paige; Karpurapu, Anish; Henry, Albert; Thomas, Michael C; McCord, Timothy J; Brezitski, Kyla; Prasad, Anil; ... Karra, Ravi; + view all (2022) Coupled myovascular expansion directs cardiac growth and regeneration. Development , 149 (18) , Article dev200654. 10.1242/dev.200654. Green open access

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Abstract

Heart 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. We 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. Our work demonstrates the importance of coupled CEC and CM expansion and reveals a myovascular niche that may be therapeutically targeted for heart regeneration.

Type: Article
Title: Coupled myovascular expansion directs cardiac growth and regeneration
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.200654
Publisher version: https://doi.org/10.1242/dev.200654
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Myovascular, Heart regeneration, Cardiomyocyte proliferation, Mouse
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Infectious Disease Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10157032
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