March 3, 2026Open Access

YBX1 promotes angiogenesis after myocardial infarction by stabilizing HIF1α mRNA via m6A signaling

Puntos clave

YBX1 is crucial for enhancing angiogenesis after myocardial infarction, promoting cardiac repair.
In vitro experiments demonstrate that YBX1 overexpression increases viability and proliferation of endothelial cells.
Observational analysis using mouse models highlights that YBX1 delivery improves cardiac function and reduces fibrosis post-MI.
This work suggests that targeting YBX1 may serve as a new option for therapeutic interventions in ischemic heart disease.

Resumen

Angiogenesis is essential for myocardial repair after myocardial infarction (MI). While Y-box binding protein 1 (YBX1) is well-established in cancer biology, its role in post-MI angiogenesis remains unknown. Here, we show that YBX1 expression is increased in endothelial cells after MI, with higher levels observed in the peri-infarct region, and is also induced in hypoxic HUVECs. In vitro, YBX1 overexpression enhances HUVEC viability, migration, and proliferation, whereas siRNA-mediated knockdown impairs these functions. In vivo, endothelial-specific AAV9-YBX1 delivery improves cardiac function, reduces fibrosis, and enhances angiogenesis in murine MI models, while AAV9-shYBX1 exacerbates cardiac injury. Mechanistically, RNA sequencing reveals that YBX1 deficiency disrupts HIF1α signaling. YBX1 interacts with IGF2BP1/3 to stabilize HIF1α mRNA via m6A modification, with YBX1 depletion accelerating HIF1α mRNA decay. Collectively, YBX1 promotes post-MI angiogenesis and cardiac repair through an m6A-dependent IGF2BP1/3-HIF1α axis, establishing YBX1 as a therapeutic target for ischemic heart disease.

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