Integrin subunit alpha 5 maintains mitochondrial function in ox-LDL-induced cardiac microvascular endothelial cells by activating the PI3K/Akt signaling pathway.

Abstract

Background: Cardiac microvascular endothelial cells (CMECs) play a pivotal role in the regulation of blood flow, and their impairment triggers a spectrum of pathological changes. Our previous study revealed a marked attenuation of CMEC dysfunction by integrin subunit alpha 5 (ITGA5), a member of the integrin protein family. This study investigated the effect of ITGA5 on mitochondrial function in CMECs and explored the underlying regulatory pathway.

Materials and methods: CMECs were stimulated with oxidized low-density lipoprotein (ox-LDL) to mimic coronary artery disease (CAD). The effects of ITGA5 on diverse aspects of CMEC behavior, including viability, apoptosis, angiogenesis, oxidative stress, and mitochondrial function, were systematically assessed. The involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway was further examined using the PI3K inhibitor LY294002.

Results: ITGA5 overexpression mitigated ox-LDL-induced injury in CMECs, as reflected by increased viability, angiogenesis, and mitochondrial function, as well as reduced apoptosis and oxidative stress. The reversal of these protective effects by the PI3K inhibitor indicates the involvement of the PI3K/Akt signaling pathway.

Conclusions: This study demonstrated that ITGA5 activates the PI3K/Akt signaling pathway to preserve mitochondrial function and attenuate ox-LDL-induced CMEC dysfunction. Therefore, targeted amelioration of this cellular injury may represent a strategically important approach to the prevention and treatment of this condition.