Journal article
Protective Role of Short-Chain Fatty Acids against Ang- II-Induced Mitochondrial Dysfunction in Brain Endothelial Cells: A Potential Role of Heme Oxygenase 2
Antioxidants, Vol.12(1), p.160
01/10/2023
DOI: 10.3390/antiox12010160
PMCID: PMC9854784
PMID: 36671022
Abstract
Objectives: Short-chain fatty acids (SCFAs), the main metabolites released from the gut microbiota, are altered during hypertension and obesity. SCFAs play a beneficial role in the cardiovascular system. However, the effect of SCFAs on cerebrovascular endothelial cells is yet to be uncovered. In this study, we use brain endothelial cells to investigate the in vitro effect of SCFAs on heme oxygenase 2 (HO-2) and mitochondrial function after angiotensin II (Ang-II) treatment. Methods: Brain human microvascular endothelial cells were treated with Ang-II (500 nM for 24 h) in the presence and absence of an SCFAs cocktail (1 μM; acetate, propionate, and butyrate) and/or HO-2 inhibitor (SnPP 5 μM). At the end of the treatment, HO-2, endothelial markers (p-eNOS and NO production), inflammatory markers (TNFα, NFκB-p50, and -p65), calcium homeostasis, mitochondrial membrane potential, mitochondrial ROS and H
2
O
2
, and mitochondrial respiration were determined in all groups of treated cells. Key Results: Our data showed that SCFAs rescued HO-2 after Ang-II treatment. Additionally, SCFAs rescued Ang-II-induced eNOS reduction and mitochondrial membrane potential impairment and mitochondrial respiration damage. On the other hand, SCFAs reduced Ang-II-induced inflammation, calcium dysregulation, mitochondrial ROS, and H
2
O
2
. All of the beneficial effects of SCFAs on endothelial cells and mitochondrial function occurred through HO-2. Conclusions: SCFAs treatment restored endothelial cells and mitochondrial function following Ang-II-induced oxidative stress. SCFAs exert these beneficial effects by acting on HO-2. Our results are opening the door for more studies to investigate the effect the of SCFAs/HO-2 axis on hypertension and obesity-induced cerebrovascular diseases.
Details
- Title: Subtitle
- Protective Role of Short-Chain Fatty Acids against Ang- II-Induced Mitochondrial Dysfunction in Brain Endothelial Cells: A Potential Role of Heme Oxygenase 2
- Creators
- Modar Kassan - University of Tennessee Health Science CenterYoungin Kwon - University of IowaUndral Munkhsaikhan - University of IowaAmal M. Sahyoun - University of IowaTauheed Ishrat - College of Dental Medicine, Lincoln Memorial University, Knoxville, TN 37917, USA Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA Department of Bioscience Research and General Dentistry, College of Dentistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA Department of Food Science and Agriculture Chemistry, McGill University, Montreal, QC H9X 3V9, Canada Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, University Rey Juan Carlos, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), ISCIII, 28922 Madrid, Spain Instituto de Química, Pontificia Universidad Católica de Valparaíso, Valparaíso 2340000, Chile Department of Pharmaceutical Sciences, School of Pharmacy, West Coast University, Los Angeles, CA 90004, USA Cardiovascular Division, Department of Medicine, Abboud Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAMaría Galán - College of Dental Medicine, Lincoln Memorial University, Knoxville, TN 37917, USA Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA Department of Bioscience Research and General Dentistry, College of Dentistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA Department of Food Science and Agriculture Chemistry, McGill University, Montreal, QC H9X 3V9, Canada Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, University Rey Juan Carlos, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), ISCIII, 28922 Madrid, Spain Instituto de Química, Pontificia Universidad Católica de Valparaíso, Valparaíso 2340000, Chile Department of Pharmaceutical Sciences, School of Pharmacy, West Coast University, Los Angeles, CA 90004, USA Cardiovascular Division, Department of Medicine, Abboud Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAAlexis A. Gonzalez - University of IowaAmmaar H. Abidi - College of Dental Medicine, Lincoln Memorial University, Knoxville, TN 37917, USA Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA Department of Bioscience Research and General Dentistry, College of Dentistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA Department of Food Science and Agriculture Chemistry, McGill University, Montreal, QC H9X 3V9, Canada Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, University Rey Juan Carlos, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), ISCIII, 28922 Madrid, Spain Instituto de Química, Pontificia Universidad Católica de Valparaíso, Valparaíso 2340000, Chile Department of Pharmaceutical Sciences, School of Pharmacy, West Coast University, Los Angeles, CA 90004, USA Cardiovascular Division, Department of Medicine, Abboud Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAAdam Kassan - University of IowaKarima Ait-Aissa - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Antioxidants, Vol.12(1), p.160
- DOI
- 10.3390/antiox12010160
- PMID
- 36671022
- PMCID
- PMC9854784
- NLM abbreviation
- Antioxidants (Basel)
- ISSN
- 2076-3921
- eISSN
- 2076-3921
- Publisher
- MDPI
- Grant note
- 7R01HL150360-02 / National Institutes of Health PI20/01004 / Instituto de Salud Carlos III (ISCIII) 2021CDA853499 / American Heart Association
- Language
- English
- Date published
- 01/10/2023
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984361725602771
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