Key result
Ischemia/reperfusion injury depletes resident cardiac macrophages by day 4 while triggering distinct transcriptomic shifts.
Why the study?
Macrophages undergo dynamic phenotypic changes after AMI and reperfusion that are critical to ventricular remodeling, fibrosis, and long-term prognoses. This study aimed to elucidate the spatiotemporal behavior of specific macrophage subtypes and identify candidate macrophage-associated transcriptional programs during early AMI.
Does myocardial ischemia/reperfusion injury alter the spatiotemporal transcriptomic signatures and population dynamics of resident cardiac macrophages in C57BL/6 mice during early acute myocardial infarction?
Does myocardial ischemia/reperfusion injury alter the spatiotemporal transcriptomic signatures and population dynamics of resident cardiac macrophages in C57BL/6 mice during early acute myocardial infarction?
p-value: p=<0.05
This preclinical study maps the spatial and temporal gene expression profiles of resident cardiac macrophages during early acute myocardial infarction, identifying candidate inflammatory, reparative, and fibrotic pathways such as S100a8/S100a9 signaling for future mechanistic investigation.
Should not change acute MI management; leaves open macrophage dynamics as targets for future translational studies.
Background Acute myocardial infarction (AMI) followed by reperfusion result in a phasic response by cardiac macrophages. During the first 7 days after AMI, macrophage populations exhibit dynamic phenotypic changes. Ultimately, inflammatory damage results in ventricular remodeling and fibrosis. Macrophages are critical to cardiac function and long-term prognoses. Objective Elucidate the spatiotemporal behavior of specific macrophage subtypes during AMI and identify candidate macrophage-associated transcriptional programs during early AMI. Methods We implemented an ischemia/reperfusion injury (IRI) mouse model of AMI to assess cardiac macrophage behavior during AMI. Resident cardiac macrophages (RCM) were isolated using flow cytometry and analyzed with NanoString. Pathway enrichment analysis annotated statistically significant genes. We employed transcriptome-wide, spatiotemporal analysis of cardiac tissue samples during AMI. Results NanoString analysis of pooled RCM samples identified candidate differentially expressed genes (DEGs) between time points, and pathway enrichment analysis suggested inflammatory, reparative, and extracellular matrix-associated programs during early AMI. Visium spatial transcriptomic analysis of cardiac tissue samples identified spatial patterns consistent with six macrophage-associated transcriptional states within the cardiac compartment. Integration of NanoString, Visium, and immunostaining data revealed temporal and spatial patterns of S100a9-associated macrophage signatures during early AMI. We also observed spatial co-localization of macrophage-associated and fibrosis-associated transcripts in injured regions. Conclusions These findings provide insight into cardiac macrophage-associated transcriptional programs during AMI and identify candidate inflammatory, reparative, and fibrosis-associated pathways for future mechanistic investigation.
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Yap et al. (2026) studied Acute myocardial infarction / myocardial ischemia-reperfusion injury (preclinical mouse model) (n=9). Ischemia/reperfusion injury via 30-minute left anterior descending coronary artery ligation followed by reperfusion vs. Non-infarcted steady-state control mouse hearts was evaluated on Spatiotemporal transcriptomic changes and absolute numbers of resident cardiac macrophages (CD45+CD64+CD11b+CCR2-MHCIILoTIMD4+LYVE1+) at 2 and 4 days post-AMI (p=<0.05). Ischemia/reperfusion injury significantly decreased resident cardiac macrophage numbers by day 4 (p<0.005) while inducing 30 differentially expressed genes at day 2 and 19 at day 4.
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