Post-MI cardiac repair: The role of angiogenesis in heart rejuvenation –Areview

Abstract

After a myocardial infarction (MI), the heart's limited regenerative capacity is outstripped by substantial myocytes degeneration and significant arterial damage. Cardiac repair involves a complex, well-coordinated sequence of events, including a strong angiogenic response in the heart's peri-infarct border zone, leading to fibroblast proliferation and scar formation. Effective vascular formation post-MI helps limit myocytes hypertrophy and reduces scar formation by decreasing collagen deposition, thus improving heart function. Robust data from conventional in vitro thrombotic approaches and animal models show that multiple synchronized signaling pathways, including Wnt, PI3K, Notch, and ion channel regulation of cytoplasmic Ca2+levels, control angiogenesis of endothelial precursor cells (EPCs) and existing endothelial cells (ECs). Factors like hypoxia, VEGF and FGF family growth factors, nitric oxide synthase, inflammation, and miRNAs are crucial in angiogenic pathways, significantly impacting the infarcted heart. Post-MI, paracrine and autocrine cell-to-cell signals, predominantly delivered by extracellular vesicles carrying pro-angiogenic proteins and non-coding RNAs like miRNAs, are vital for cardiac repair. This review overviews major angiogenic pathways and their effects on post-infarction myocardial angiogenesis, emphasizing the roles of endothelial nitric oxide synthase and growth factors like VEGF and FGF. It also explores signaling pathways triggered by MI, focusing on ROS regulation, Ca2+influx, and miRNAs in endothelial cell activation and subsequent angiogenesis. Additionally, the review discusses troponin's role as a biomarker for myocardial infarction, highlighting its function as a potent angiogenesis inhibitor.