Aims: Cardiovascular disease (CVD) is the leading cause of death worldwide. Inflammation and oxidative stress are the primary factors underlying angiotensin II (Ang II)-induced aortic damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important antioxidative stress factor. Sulforaphane (SFN), which is naturally found in cruciferous vegetables, is an Nrf2 agonist that is safe for oral administration. Here, we aimed to explore the potential of SFN in protecting against Ang II-induced aortic damage by upregulating Nrf2 expression via the extracellular signal-regulated kinase (ERK)/glycogen synthase kinase-3 beta (GSK-3β)/Fyn pathway.
Main methods and key findings: Wild-type (WT) C57BL/6J and Nrf2-knockout (Nrf2-KO) mice were injected with Ang II to induce aortic inflammation, oxidative stress, and cardiac remodeling (increased fibrosis and wall thickness). SFN treatment prevented aortic damage via Nrf2 activation in the WT mice. However, the protective effect of SFN on Ang II-induced aortic damage and upregulation of genes downstream of Nrf2 were not observed in Nrf2-KO mice. SFN induced the upregulation of aortic Nrf2 and inhibited the accumulation of ERK, GSK-3β, and Fyn in the nuclei.
Significance: These results revealed that Nrf2 plays a central role in protecting against Ang II-induced aortic injury. Furthermore, SFN prevented Ang II-induced aortic damage by activating Nrf2 through the ERK/GSK-3β/Fyn pathway.
Keywords: Angiotensin II; Aortic damage; Nuclear factor erythroid 2-related factor; Oxidative stress; Sulforaphane.
Copyright © 2022 Elsevier Inc. All rights reserved.