Multicellular Communication Networks in Myocardial Ischemia-Reperfusion Injury: Spatial and Temporal Organization of Injury and Repair
- 1Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210096, China
Abstract
Myocardial ischemia–reperfusion injury (MIRI) complicates recovery after acute myocardial infarction despite timely restoration of coronary blood flow. Beyond cardiomyocyte-intrinsic oxidative stress, calcium dysregulation, mitochondrial injury, and regulated cell death, reperfusion simultaneously reorganizes communication among multiple cardiac and extracardiac cell populations. Single-cell and spatial multiomic studies further reveal marked spatial and temporal heterogeneity across the injured heart, although the causal intercellular mechanisms underlying many associations remain incompletely defined. In this Review, we examine MIRI through a multicellular communication framework and discuss interactions among cardiomyocytes, immune cells, endothelial cells, platelets, fibroblasts, vascular mural cells, and extracardiac tissues across the infarct core, border zone, coronary microvascular unit, and remote myocardium. Communication occurs through soluble danger and inflammatory signals, selected metabolites, extracellular vesicles, extracellular matrix and mechanical cues, and direct contact or junctional mechanisms. We distinguish experimentally supported intercellular pathways from spatial associations, parallel responses, and indirect regulatory mechanisms. A spatiotemporally resolved view of these networks may help identify interactions that amplify injury, impair microvascular reperfusion, or participate in resolution and repair, while guiding selective interventions that limit pathological signaling without compromising tissue recovery.
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BibTeX
@article{wang2026multicellular,
title = {{Multicellular Communication Networks in Myocardial Ischemia-Reperfusion Injury: Spatial and Temporal Organization of Injury and Repair}},
author = {Yiming Wang and Yuxuan Luo},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15201869},
url = {https://www.mdpi.com/2073-4409/15/20/1869},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multicellular Communication Networks in Myocardial Ischemia-Reperfusion Injury: Spatial and Temporal Organization of Injury and Repair
AU - Yiming Wang
AU - Yuxuan Luo
PY - 2026
DA - 2026/10/14
JO - Cells
DO - 10.3390/cells15201869
UR - https://www.mdpi.com/2073-4409/15/20/1869
AB - Myocardial ischemia–reperfusion injury (MIRI) complicates recovery after acute myocardial infarction despite timely restoration of coronary blood flow. Beyond cardiomyocyte-intrinsic oxidative stress, calcium dysregulation, mitochondrial injury, and regulated cell death, reperfusion simultaneously reorganizes communication among multiple cardiac and extracardiac cell populations. Single-cell and spatial multiomic studies further reveal marked spatial and temporal heterogeneity across the injured heart, although the causal intercellular mechanisms underlying many associations remain incompletely defined. In this Review, we examine MIRI through a multicellular communication framework and discuss interactions among cardiomyocytes, immune cells, endothelial cells, platelets, fibroblasts, vascular mural cells, and extracardiac tissues across the infarct core, border zone, coronary microvascular unit, and remote myocardium. Communication occurs through soluble danger and inflammatory signals, selected metabolites, extracellular vesicles, extracellular matrix and mechanical cues, and direct contact or junctional mechanisms. We distinguish experimentally supported intercellular pathways from spatial associations, parallel responses, and indirect regulatory mechanisms. A spatiotemporally resolved view of these networks may help identify interactions that amplify injury, impair microvascular reperfusion, or participate in resolution and repair, while guiding selective interventions that limit pathological signaling without compromising tissue recovery.
SN - 2073-4409
ER -