Stroke-induced cardiac immune remodeling may influence cardiac outcomes in subsequent myocardial infarction

Background The risk of acute myocardial infarction (AMI) increases markedly following acute ischemic stroke (AIS), peaking within the first month. Despite this elevated risk, effective therapeutic strategies for patients with post-stroke AMI remain limited. Although stroke has been shown to induce long-term remodeling of the cardiac immune microenvironment, acute-phase cardiac immune changes after AIS have not been systematically characterized. Methods We conducted a cross-species transcriptomic analysis to compare acute immune responses in AIS and AMI. Public peripheral blood bulk RNA-seq datasets from AIS and AMI patients (GSE202518, GSE60993) were analyzed for differential gene expression and GO/KEGG pathway enrichment. In mice, peripheral blood single-cell RNA-seq datasets from middle cerebral artery occlusion (MCAO) and myocardial infarction models (GSE225948, GSE227189) were analyzed to characterize immune cell phenotypes. Cardiac tissue bulk RNA-seq datasets (GSE102558, GSE46395) were analyzed for differential gene expression and GO/KEGG pathway enrichment, with immune cell infiltration inferred using CIBERSORT. Results Both human and murine peripheral blood exhibited acute inflammatory activation in AIS and AMI, which was more pronounced in AMI. In murine cardiac tissue, AMI induced robust inflammatory activation at 24 hours, including enrichment of IL-17, TNF, and NF-κB pathways, increased neutrophil infiltration, and M1 macrophage polarization, consistent with a typical acute inflammatory response pattern. In contrast, at 24 hours post-MCAO, cardiac tissue showed limited inflammatory activation and downregulation of antigen presentation and phagocytosis pathways. At 72 hours post-MCAO, repair-associated features emerged, including increased M2 macrophages, while inflammatory activation remained low. Glucocorticoid response pathways were significantly enriched. Overall, AIS induced a cardiac immune state characterized by restrained inflammation and early repair engagement, distinct from the robust inflammatory activation observed in AMI. Conclusion Acute ischemic stroke remodels the cardiac immune microenvironment during the acute phase, resulting in an inflammation-constrained, repair-oriented state. This immune state may alter the inflammatory and reparative responses to subsequent AMI and affect cardiac remodeling. Post-stroke AMI may therefore represent a pathophysiologically distinct subtype with a unique immune background, supporting further investigation into risk stratification and targeted therapeutic strategies.