Lymphoangiocrine signals promote cardiac growth and repair

Xiaolei Liu, Ester De la Cruz, Xiaowu Gu, Laszlo Balint, Michael Oxendine-Burns, Tamara Terrones, Wanshu Ma, Hui Hsuan Kuo, Connor Lantz, Trisha Bansal, Edward Thorp, Paul Burridge, Zoltán Jakus, Joachim Herz, Ondine Cleaver, Miguel Torres, Guillermo Oliver*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Recent studies have suggested that lymphatics help to restore heart function after cardiac injury1–6. Here we report that lymphatics promote cardiac growth, repair and cardioprotection in mice. We show that a lymphoangiocrine signal produced by lymphatic endothelial cells (LECs) controls the proliferation and survival of cardiomyocytes during heart development, improves neonatal cardiac regeneration and is cardioprotective after myocardial infarction. Embryos that lack LECs develop smaller hearts as a consequence of reduced cardiomyocyte proliferation and increased cardiomyocyte apoptosis. Culturing primary mouse cardiomyocytes in LEC-conditioned medium increases cardiomyocyte proliferation and survival, which indicates that LECs produce lymphoangiocrine signals that control cardiomyocyte homeostasis. Characterization of the LEC secretome identified the extracellular protein reelin (RELN) as a key component of this process. Moreover, we report that LEC-specific Reln-null mouse embryos develop smaller hearts, that RELN is required for efficient heart repair and function after neonatal myocardial infarction, and that cardiac delivery of RELN using collagen patches improves heart function in adult mice after myocardial infarction by a cardioprotective effect. These results highlight a lymphoangiocrine role of LECs during cardiac development and injury response, and identify RELN as an important mediator of this function.

Original languageEnglish (US)
Pages (from-to)705-711
Number of pages7
JournalNature
Volume588
Issue number7839
DOIs
StatePublished - Dec 24 2020

ASJC Scopus subject areas

  • General

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