Protective role of short chain fatty acids against Angiotensin II-induced mitochondrial dysfunction in brain endothelial cells: Potential role of Heme Oxygenase 2

Abstract

Objectives: Short chain fatty acids (SCFAs), the main metabolites released from the gut microbiota, are reduced during hypertension. SCFAs play a beneficial role on the cardiovascular system. However, the effect of SCFAs on cerebrovascular endothelial cells is yet to be uncovered. In this study, we used brain endothelial cells to investigate the in vitro effect of SCFAs on heme oxygenase 2 (HO-2) and mitochondrial function following Angiotensin-II treatment. Methods: Brain human microvascular endothelial cells were treated with Angiotensin II (Ang-II, 500nM for 24hours) in the presence and absence of SCFAs cocktail (1mM; acetate, propionate, and butyrate) and/or HO-2 inhibitor (SnPP 5 μM). At the end of the treatment, HO-2, endothelial markers (p-eNOS, NO production), inflammatory markers (TNFα, NFkB-p50 and -p65), calcium homeostasis, mitochondrial membrane potential, mitochondrial ROS and hydrogen peroxide (H 2 O 2 ), and mitochondrial respiration were determined in all groups of treated cells. Results: Our data showed that SCFAs rescued HO-2 after Angiotensin II treatment. Additionally, SCFAs rescued Angiotensin II-induced eNOS reduction, mitochondrial membrane potential impairment and mitochondrial respiration damage. On the other hand, SCFAs reduced Angiotensin II-induced inflammation, calcium dysregulation, mitochondrial ROS, and H 2 O 2 . All these beneficial effects of SCFAs on endothelial cells and mitochondrial function occurred through HO-2. Conclusions: SCFAs treatment restored endothelial cells and mitochondrial function following Angiotensin II-induced oxidative stress. SCFAs exert these beneficial effects by acting on HO-2. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.