Pre-emptive Post-Reperfusion Cardioprotection with a Small Molecule in Rodents that Suppresses Genes Predictive of Heart Failure in Reperfused STEMI Patients

We determined the post-reperfusion cardioprotective properties of BT2 in rat models of M/IR injury. Single nucleus RNA-seq of the AAR revealed that BT2 modulated the expression of key regulators of heart function, inflammation, extracellular matrix production and fibrosis, particularly in macrophages and myofibroblasts. Bulk RNA-seq showed BT2 downregulated multiple genes in the AAR associated with disease severity in ACS patients as well as genes predictive of HF in ST-elevation myocardial infarction (STEMI) patients undergoing PCI, including cytokines, inflammasome, damage-associated molecular patterns (DAMPs), DAMP-sensing receptors and biomarkers of HF.