Coronary endothelial cells undergo venous-enriched disrupted maturation following myocardial infarction.

Authors

Kaitlyn Ford, Hosanna Abbay, Amy S Leonardson, Jennifer M Franks, Nicholas W Chavkin

Published in

Basic research in cardiology. Jun 13, 2026. Epub Jun 13, 2026.

Abstract

The coronary microvascular plexus responds to cardiac ischemia through angiogenic neovascularization in the ischemic and border zones to sustain the demand for oxygen and nutrients. Although new blood vessels form, the process of endothelial maturation and extent to which the post-injured microvascular plexus resembles the pre-injured state is unclear. Developmental processes suggest that neovascular endothelial cells must specify toward arterial or venous fates to generate a continuum of heterogenous identities across the microvascular plexus. Therefore, we investigated whether coronary endothelial cells undergo similar arterial-venous specification after ischemia and return to a pre-injured maturation state. Cardiac single-cell RNA sequencing datasets from a murine myocardial infarction model isolated over time post-injury were analyzed for endothelial cell fate dynamics through gene expression and cell trajectory. We found that murine coronary endothelial cells undergo arterial-venous specification at later time points following ischemia-induced angiogenesis. However, post-injured endothelial cells express a reduction of genes associated with arterial-venous identity and blood vessel development with early dysregulation of signaling pathways required for arterial-venous specification. These transcriptional changes are associated with disrupted heterogeneity of the post-injured microvascular plexus and a shift toward venous fate. Endothelial cells in cardiac tissue of ischemic cardiomyopathy patients also mirror the disrupted gene patterns, signaling pathways, and venous-shifted heterogeneity. Using primary human coronary microvascular endothelial cells, we identified that arterial identity is promoted by TGF signaling and inhibited by WNT signaling. Finally, spatial sequencing datasets from human ischemic cardiomyopathy of different injured cardiac zones identified that the venous-shifted maturation state is enriched in the border zone and associates with POSTN expression. These results suggest that the post-injured coronary microvascular plexus is driven to a venous-shifted fate in the border zone, revealing disrupted arterial-venous heterogeneity as a potential hallmark of ischemic heart failure.

PMID:
42287426
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.

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