Endothelin-1 Promotes Perivascular Adipose Tissue Dysfunction In Obese Mice Fed A High-Fat Diet Via Down-Regulation Of NRF2 And Oxidative Stress

Obesity is a chronic pathophysiological condition that results in a greater propensity to develop cardiovascular diseases. Perivascular adipose tissue (PVAT) regulates vascular tone under physiological conditions. However, in obesity, functional changes occur in this tissue that result in oxidative stress, favoring the release of vasoconstrictor substances. The production of reactive oxygen species (ROS) in the vasculature is mediated by different stimuli, including endothelin-1 (ET-1), a peptide that promotes a balance between vasoconstrictor and vasodilator responses. Among the intracellular signaling pathways capable of neutralizing ROS, nuclear factor 2-related transcriptional factor E2 (NRF2) promotes the transcription of antioxidant genes.