Knockdown of VNN1 protects cardiac myoblasts from hypoxia/reoxygenation injury via the PI3K/Akt pathway.

Abstract

Myocardial ischemia/reperfusion (I/R) injury is a critical factor contributing to adverse outcomes following infarction, primarily due to oxidative stress, inflammation, and cardiomyocyte death. Vanin-1 (VNN1), a pantetheinase enzyme involved in redox regulation, has recently emerged as a potential mediator of tissue damage under stress conditions. This study aimed to investigate the role of VNN1 in hypoxia/reoxygenation (H/R)-induced injury in H9c2 cardiomyocytes and to explore the involvement of the PI3K/Akt axis. An in vitro H/R model was established using H9c2 cells, and VNN1 knockdown was achieved via shRNA. Cellular injury, inflammation, and oxidative stress were assessed using viability assays, LDH release, ELISA, ROS detection, and biochemical analysis. Results revealed that VNN1 expression was significantly upregulated in H/R-treated cells. Silencing VNN1 mitigated cell damage, reduced pro-inflammatory cytokine release, and alleviated oxidative stress. Mechanistically, these protective effects were dependent on activation of the PI3K/Akt signaling axis, as inhibition of this pathway reversed the benefits of VNN1 knockdown. In conclusion, VNN1 knockdown confers protection against H/R-induced cardiomyocyte injury via activating the PI3K/Akt pathway, highlighting VNN1 as a potential target for myocardial I/R injury.