Abstract
Myocardial infarction (MI) initiates a cascade of biological changes ending in cardiac remodeling and heart failure. Recent studies have characterized transcriptional programs in post-infarct remodeling, focusing on discrete timepoints. This study adopted a complementary approach by constructing a temporal map of gene expression changes from minutes to weeks post-myocardial infarction. Two mouse RNA-sequencing datasets were integrated, covering post-infarction timepoints from 10 min to 28 days. Expression data were analyzed using clustering, functional enrichment, and network-based hub gene analysis to define distinct gene expression modules. Nine clusters were identified, including immune activation, extracellular matrix remodeling, mitochondrial dysfunction, and circadian rhythm disruption. Immune signatures peaked between 1 and 72 h post-MI, fibrotic remodeling and cell proliferation dominated the 3-7-day window, and fibrosis still extended to the 28-day mark. Mitochondrial dysfunction persisted into the 28th day, along with circadian rhythm and metabolic dysfunction. These trajectories highlight distinct pathways and the potential therapeutic windows across infarction. This research offers a timeline for temporally guided therapies in MI. Identifying distinct pathways and hub genes to provide a molecular basis for future studies targeting inflammation, fibrosis, metabolism, and chronobiology. These results may accelerate the development of more effective treatments for myocardial infarction.