Spatiotemporal transcriptomic signatures of resident cardiac macrophages and macrophage-associated spatial states during acute myocardial infarction
Year: 2026
Type: article
Abstract: 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.
Source: Frontiers in Immunology
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223064520