Sodium tanshinone IIA sulfonate suppresses heat stress-induced endothelial cell apoptosis by promoting NO production through upregulating the PI3K/AKT/eNOS pathway.

Abstract

Heat shock is a life-threatening disease involving systematic inflammation that is closely related to endothelial injury and can lead to multiple organ dysfunction syndrome. Sodium tanshinone IIA sulfonate (STS) has various functions in the vascular endothelium. In the present study, STS is presented to suppress heat stress‑induced apoptosis of human umbilical vein endothelial cells (HUVECs) and high ambient temperature‑induced systematic inflammation in Sprague Dawley rats. In addition, the STS apoptosis‑suppression mechanism was explored. The results presented in the present study demonstrated that the PI3K/AKT pathway was stimulated by STS treatment and that eNOS phosphorylation at Ser‑1177 was also upregulated, resulting in increased nitric oxide production in HUVECs under heat stress. Using specific inhibitors, the authors confirmed that STS‑induced endothelial nitric oxide synthase (eNOS) phosphorylation at Ser‑1177 was activated by protein kinase B phosphorylation at Ser‑473, involving activation of phosphatidylinositol‑3 kinase (PI3K). The results suggested that STS suppresses heat stress‑induced apoptosis of HUVECs via the PI3K/AKT/eNOS pathway and may be used in heat shock treatment as a vascular endothelial protection mechanism.