Protective Role of Short-Chain Fatty Acids against Ang- II-Induced Mitochondrial Dysfunction in Brain Endothelial Cells: A Potential Role of Heme Oxygenase 2.
Protective Role of Short-Chain Fatty Acids against Ang- II-Induced Mitochondrial Dysfunction in Brain Endothelial Cells: A Potential Role of Heme Oxygenase 2.
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DOI：
10.3390/antiox12010160
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发表时间：
2023-01-10
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目的：短链脂肪酸（SCFAs），从肠道微生物群释放的主要代谢产物，在高血压和肥胖期间发生改变。SCFA在心血管系统中发挥有益作用。然而，SCFAs对脑血管内皮细胞的影响尚未被发现。在这项研究中，我们使用脑内皮细胞研究在血管紧张素II（Ang-II）治疗后，SCFAs对血红素加氧酶2（HO-2）和线粒体功能的体外影响。研究方法：在存在和不存在SCFAs混合物（1 μM;乙酸盐、丙酸盐和丁酸盐）和/或HO-2抑制剂（SnPP 5 μM）的情况下，用Ang-II（500 nM，持续24 h）处理脑人微血管内皮细胞。处理结束时，测定所有处理组细胞中的HO-2、内皮标志物（p-eNOS和NO产生）、炎症标志物（TNFα、NFκB-p50和-p65）、钙稳态、线粒体膜电位、线粒体ROS和H2 O2以及线粒体呼吸。关键结果：我们的数据显示，SCFAs在Ang-II治疗后拯救HO-2。此外，SCFAs挽救了Ang-II诱导的eNOS减少和线粒体膜电位损伤以及线粒体呼吸损伤。另一方面，SCFAs减少Ang-II诱导的炎症、钙失调、线粒体ROS和H2 O2。SCFAs对内皮细胞和线粒体功能的所有有益作用均通过HO-2发生。结论：SCFAs治疗恢复血管生成素II诱导的氧化应激后的内皮细胞和线粒体功能。SCFA通过作用于HO-2发挥这些有益作用。本研究结果为进一步研究SCFAs/HO-2轴在高血压和肥胖性脑血管病中的作用提供了基础。
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 H2O2, 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 H2O2. 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.
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影响因子：
3.7
作者：
Kesavan R;Potunuru UR;Nastasijević B;T A;Joksić G;Dixit M
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通讯作者：
Perry, George
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Anrather J
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