YBX1 Drives Post-Myocardial Infarction Angiogenesis via an m6A-IGF2BP1/3-Dependent Stabilization of HIF-1a mRNA

Angiogenesis plays a vital role in myocardial repair following myocardial infarction (MI). Y-box binding protein 1 (YBX1), an RNA-binding protein known for its role in cancer, is found to be significantly upregulated in endothelial cells within the peri-infarct zone and in hypoxic human umbilical vein endothelial cells (HUVECs). Using in vitro and in vivo models, we demonstrate that YBX1 enhances endothelial cell viability, proliferation, migration, and tube formation. Endothelial-specific overexpression of YBX1 in a murine MI model improved cardiac function and angiogenesis, while YBX1 knockdown aggravated cardiac injury. Transcriptome (RNA-seq) analysis revealed that YBX1 deficiency disrupts HIF-1a signaling. Mechanistically, YBX1 forms a complex with IGF2BP1/3 to stabilize HIF-1a mRNA through N6-methyladenosine (m6A) modification, thereby promoting angiogenesis and cardiac repair.