Histochemical characterization of TDAG51 in endothelial remodeling and angiogenesis following myocardial infarction via PI3K-AKT signaling.

Myocardial infarction (MI) triggers complex cardiac remodeling, including endothelial dysfunction, fibrosis, and angiogenesis. Characterizing the spatial distribution and cellular localization of regulatory molecules is critical for understanding cardiac repair mechanisms. This study investigated the histochemical localization and functional role of T-cell death-associated gene 51 (TDAG51) in endothelial cells during post-MI angiogenesis and cardiac remodeling. We established a murine MI model and silenced TDAG51 with adeno-associated virus. Histochemical assays were used to determine TDAG51 localization and its relation to vascular density, and Masson staining was used to evaluate myocardial fibrosis. In vitro, we exposed human coronary artery endothelial cells (HCAECs) to oxygen-glucose deprivation (OGD) to examine TDAG51 expression and endothelial function. We performed Western blot and transcriptomic analyses to explore the involvement of the PI3K-AKT signaling pathway. Histochemical analyses revealed that TDAG51 was predominantly localized in CD31-positive endothelial cells and was significantly upregulated in the infarcted myocardium, particularly in the peri-infarct regions. TDAG51 silencing markedly increased capillary density and reduced fibrotic area, as demonstrated by immunohistochemistry and Masson staining. In vitro, TDAG51 knockdown enhanced endothelial proliferation, migration, and tube formation. Mechanistically, these effects were associated with activation of the PI3K-AKT signaling pathway, while pharmacological inhibition of PI3K attenuated the pro-angiogenic phenotype. This study provides histochemical evidence that TDAG51 is enriched in ischemic myocardial endothelial cells and negatively regulates angiogenesis. TDAG51 inhibition promotes vascular remodeling and enhances cardiac repair following myocardial infarction, highlighting TDAG51 as a promising therapeutic target for improving post-MI recovery.