Integrative approach combining temporal bulk transcriptomics and single-cell RNA sequencing reveals cardioprotective effects of Suxiao Jiuxin Pill on myocardial infarction

Targeting immune-inflammatory responses in myocardial infarction (MI) has emerged as a promising strategy, but the highly dynamic and complex interactions among diverse immune cell populations limit the efficacy. Suxiao Jiuxin Pill (SJP), a classical traditional Chinese medicine (TCM) formulation, has been widely used to treat MI. However, the precise mechanisms of action remain poorly understood, particularly with respect to immune regulation across distinct post-infarction healing phases and at single-cell resolution. In this study, we first employed temporal bulk RNA sequencing and targeted metabolomics to delineate the transcriptional dynamics regulated by SJP during the cardiac repair process post-MI. Then, the single-cell RNA sequencing (scRNA-seq) was applied to comprehensively dissect the impact of SJP on the immune microenvironment of the infarcted heart. Temporal bulk transcriptomic analyses suggested that SJP promotes post-MI repair by enhancing angiogenesis, suppressing inflammation, and reprogramming myocardial energy metabolism. The scRNA-seq further revealed that SJP remodeled macrophage subset composition, enhancing both the abundance and reparative function of the Prg4 + macrophage subset. Moreover, SJP reprogrammed neutrophil subset composition and metabolic state, while restoring Treg/Th17 balance and B-cell homeostasis. Thus, the significant cardioprotective effects of SJP are primarily achieved by reprogramming the cardiac immune cell landscape after MI and facilitating the transition from inflammatory response to reparative phenotype. These findings suggest that leveraging the multi-component properties of TCM to restore the homeostasis of the cardiac immune microenvironment might provide a promising novel strategy for facilitating the transition from inflammation to tissue repair following MI.