Therapeutic peptide targeting oxidative stress and inflammation enhances cardiac repair and vascular regeneration after MI

Abstract Background and Aims Post-myocardial infarction (MI) inflammation, oxidative injury, and impaired angiogenesis drive adverse ventricular remodeling and contribute to heart failure progression. Therapies capable of simultaneously modulating these pathological processes may improve long-term cardiac outcomes. We evaluated a novel Multifunctional Peptide (MFP) with antioxidant, anti-inflammatory, and pro-angiogenic properties for its cardioprotective potential following MI. Methods and Results Adult rats underwent left anterior descending (LAD) coronary artery ligation and received intramyocardial MFP or vehicle. Cardiac function and structural remodeling were assessed 4 weeks post-MI by echocardiography and histopathology. MFP treatment significantly improved left ventricular systolic function, reduced cardiomyocyte apoptosis, and attenuated interstitial fibrosis compared with controls. Capillary density increased markedly in MFP-treated hearts, accompanied by reduced pro-inflammatory macrophage infiltration and a shift toward reparative M2 macrophage polarization. In vitro, MFP protected cardiomyocytes from oxidative damage and promoted M2 differentiation in macrophages. RNA-sequencing of peri-infarct tissue revealed downregulation of pathways related to necrosis and maladaptive remodeling, together with upregulation of gene networks supporting tissue repair, angiogenesis, and immune modulation. Conclusion MFP confers strong cardioprotective effects after MI through coordinated suppression of oxidative stress and inflammation and enhancement of angiogenesis. These findings highlight MFP as a promising preventive-cardiology–oriented therapeutic candidate for limiting post-MI remodeling and improving cardiac recovery.For image description, please refer to the figure legend and surrounding text.