Sulforaphane attenuates angiotensin II-induced human umbilical vein endothelial cell injury by modulating ROS-mediated mitochondrial signaling.

Abstract

The study aimed to investigate whether sulforaphane (SFN) protects against angiotensin II (Ang II)-mediated human umbilical vein endothelial cell (HUVEC) injury. Ang II treatment decreased HUVEC viability, increased cell apoptosis, decreased mitochondria membrane potential (MMP), impaired cytochrome c release, activated caspase 3/9, and induced reactive oxygen species (ROS) production, and nicotinamide adenine dinucleotide phosphate oxidase activity. Moreover, SFN treatment blunted Ang II-stimulated oxidative stress and mitochondria-related apoptosis in HUVECs. The ROS scavenger N-acetyl-l-cysteine reduced Ang II-induced oxidative stress and apoptosis, indicating that ROS generation is involved in the Ang II-induced mitochondria-mediated apoptotic pathway. SFN induced nuclear factor erythroid 2 (Nrf2) activation and expression in Ang II-stimulated HUVECs. Downregulation of Nrf2 expression by a target-specific siRNA revealed an Nrf2-dependent effect on the SFN-mediated attenuation of Ang II-induced apoptosis in HUVECs. Pretreatment with brusatol, an Nrf2-specific inhibitor, reversed the protective effects of SFN on Ang II-induced HUVEC injury. SFN treatment protected HUVECs from Ang II-induced damage by decreasing oxidative stress and ameliorating mitochondrial injury.