The role of Vav3 expression for inflammation and cell death during experimental myocardial infarction

Myocardial Infarction (MI) is the leading cause of chronic heart failure. Previous studies have suggested that Vav3, a receptor protein tyrosine kinase signal transducer, is associated with a variety of cellular signaling processes such as cell morphology regulation and cell transformation with oncogenic activity. However, the mechanism of Vav3-mediated MI development requires further investigation.

Here, The authors established an MI rat model by ligating the anterior descending branch of the left coronary artery, and an MI cell model by treating cardiomyocytes with H₂O₂. Microarray analysis was conducted to identify genes with differential expression in heart tissues relevant to MI occurrence and development. Vav3 was thus selected for further investigation.

Vav3 downregulation was observed in MI heart tissue and H₂O₂-treated cardiomyocytes. Administration of Lentiviral Vav3 (LV-VAV3) in MI rats upregulated Vav3 expression in MI heart tissue. Restoration of Vav3 expression reduced infarct area and ameliorated cardiac function in MI rats. Cardiac inflammation, apoptosis, and upregulation of NFκB signal in heart tissue of MI animals were assessed using ELISA, TUNEL staining, real-time PCR, and WB. Vav3 overexpression reduced cardiac inflammation and apoptosis and inhibited NFκB expression and activation. Betulinic Acid (BA) was then used to re-activate NFκB in Vav3-overexpressed and H₂O₂-induced cardiomyocytes. The expression of P50 and P65, as well as nuclear P65, was significantly increased by BA exposure.

Vav3 might serve as a target to reduce ischemia damage by suppressing the inflammation and apoptosis of cardiomyocytes.