Tracing the origins of de novo coronary collateral formation in cardiac repair

Coronary collateral arteries have been proposed to form de novo through artery reassembly, a process in which arterial endothelial cells (ECs) migrate away from preexisting arteries and reassemble into new arteries. Using genetic tools that trace arterial ECs, we found that their contribution to collaterals is modest. Dual genetic lineage tracing revealed that capillary ECs, rather than arterial ECs, serve as the major building blocks for de novo collaterals. The capillary-to-collateral conversion is functionally crucial for cardiac repair. In addition, transient Vegfa expression through modified messenger RNA markedly promoted collateral formation. Mechanistically, vascular endothelial growth factor (VEGF) drives arterialization by regulating HES1 transcription through YY1/SETD1A-mediated H3K4 trimethylation. Collectively, these findings redefine the cellular origin and mechanism of coronary collateral formation and highlight its role in facilitating efficient cardiac repair.

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Publication Details

Journal
Science
Published
2026-08-20
DOI
https://doi.org/10.1126/science.ady3027
Primary Topic
Congenital heart defects research
Type
article
Field-Weighted Citation Impact
0.00

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article

Tracing the origins of de novo coronary collateral formation in cardiac repair

Xiuzhen Huang, Zixin Liu, Maoying Han, Yangfeng Hou et al.
Science
Congenital heart defects research
article

Tracing the origins of de novo coronary collateral formation in cardiac repair

Xiuzhen Huang, Zixin Liu, Maoying Han, Yangfeng Hou, Kathy O. Lui, Xin Ma, Qing‐Dong Wang, Bin Zhou, Hang Qu, Cheng Kiu Ho, Mingjun Zhang, Yilian Wang
article en

Abstract

Coronary collateral arteries have been proposed to form de novo through artery reassembly, a process in which arterial endothelial cells (ECs) migrate away from preexisting arteries and reassemble into new arteries. Using genetic tools that trace arterial ECs, we found that their contribution to collaterals is modest. Dual genetic lineage tracing revealed that capillary ECs, rather than arterial ECs, serve as the major building blocks for de novo collaterals. The capillary-to-collateral conversion is functionally crucial for cardiac repair. In addition, transient Vegfa expression through modified messenger RNA markedly promoted collateral formation. Mechanistically, vascular endothelial growth factor (VEGF) drives arterialization by regulating HES1 transcription through YY1/SETD1A-mediated H3K4 trimethylation. Collectively, these findings redefine the cellular origin and mechanism of coronary collateral formation and highlight its role in facilitating efficient cardiac repair.

ScienceVol. 393(6813)
Jiangnan University (CN), Chinese University of Hong Kong (HK), ShanghaiTech University (CN), Prince of Wales Hospital (CN), Center for Excellence in Molecular Cell Science (CN), AstraZeneca (Finland) (FI), AstraZeneca (Sweden) (SE), University of Chinese Academy of Sciences (CN), University of Hong Kong (HK)
National Natural Science Foundation of China
Good health and well-being
Openalex Percentile: Top 17%
Congenital heart defects research
DOISourceOpenAlex
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