{"title":"高密度脂蛋白通过抗氧化能力保护血管内皮细胞免受硫酸吲哚酯的损伤。","authors":"Ching Chen, Chia-Chi Chang, I-Ta Lee, Chun-Yao Huang, Feng-Yen Lin, Shing-Jong Lin, Jaw-Wen Chen, Ting-Ting Chang","doi":"10.1080/15384101.2023.2296184","DOIUrl":null,"url":null,"abstract":"<p><p>Chronic kidney disease (CKD) patients have a high risk of cardiovascular disease. Indoxyl sulfate (IS) is a uremic toxin that has been shown to inhibit nitric oxide production and cause cell senescence by inducing oxidative stress. High-density lipoprotein (HDL) has a protective effect on the cardiovascular system; however, its impacts on IS-damaged endothelial cells are still unknown. This study aimed to explore the effects of exogenous supplement of HDL on vascular endothelial cells in a uremia-mimic environment. Tube formation, migration, adhesion, and senescence assays were used to evaluate the cell function of human aortic endothelial cells (HAECs). Reactive oxygen species generation was measured by using Amplex red assay. L-NAME and MCI186 were used as a nitric oxide synthase inhibitor and a free radical scavenger, respectively. HDL exerted anti-inflammatory and antioxidant effects via HIF-1α/HO-1 activation and IL-1β/TNF-α/IL-6 inhibition in IS-stimulated HAECs. HDL improved angiogenesis ability through upregulating Akt/eNOS/VEGF/SDF-1 in IS-stimulated HAECs. HDL decreased endothelial adhesiveness via downregulating VCAM-1 and ICAM-1 in IS-stimulated HAECs. Furthermore, HDL reduced cellular senescence via upregulating SIRT1 and downregulating p53 in IS-stimulated HAECs. Importantly, the above beneficial effects of HDL were mainly due to its antioxidant ability. In conclusion, HDL exerted a comprehensive protective effect on vascular endothelial cells against damage from IS through its antioxidant ability. The results of this study might provide a theoretical basis for potential HDL supplementation in CKD patients with endothelial damage.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802207/pdf/","citationCount":"0","resultStr":"{\"title\":\"High-density lipoprotein protects vascular endothelial cells from indoxyl sulfate insults through its antioxidant ability.\",\"authors\":\"Ching Chen, Chia-Chi Chang, I-Ta Lee, Chun-Yao Huang, Feng-Yen Lin, Shing-Jong Lin, Jaw-Wen Chen, Ting-Ting Chang\",\"doi\":\"10.1080/15384101.2023.2296184\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Chronic kidney disease (CKD) patients have a high risk of cardiovascular disease. Indoxyl sulfate (IS) is a uremic toxin that has been shown to inhibit nitric oxide production and cause cell senescence by inducing oxidative stress. High-density lipoprotein (HDL) has a protective effect on the cardiovascular system; however, its impacts on IS-damaged endothelial cells are still unknown. This study aimed to explore the effects of exogenous supplement of HDL on vascular endothelial cells in a uremia-mimic environment. Tube formation, migration, adhesion, and senescence assays were used to evaluate the cell function of human aortic endothelial cells (HAECs). Reactive oxygen species generation was measured by using Amplex red assay. L-NAME and MCI186 were used as a nitric oxide synthase inhibitor and a free radical scavenger, respectively. HDL exerted anti-inflammatory and antioxidant effects via HIF-1α/HO-1 activation and IL-1β/TNF-α/IL-6 inhibition in IS-stimulated HAECs. HDL improved angiogenesis ability through upregulating Akt/eNOS/VEGF/SDF-1 in IS-stimulated HAECs. HDL decreased endothelial adhesiveness via downregulating VCAM-1 and ICAM-1 in IS-stimulated HAECs. Furthermore, HDL reduced cellular senescence via upregulating SIRT1 and downregulating p53 in IS-stimulated HAECs. Importantly, the above beneficial effects of HDL were mainly due to its antioxidant ability. In conclusion, HDL exerted a comprehensive protective effect on vascular endothelial cells against damage from IS through its antioxidant ability. 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引用次数: 0
摘要
慢性肾脏病(CKD)患者罹患心血管疾病的风险很高。硫酸吲哚啶(IS)是一种尿毒症毒素,已被证明可抑制一氧化氮的产生,并通过诱导氧化应激导致细胞衰老。高密度脂蛋白(HDL)对心血管系统有保护作用,但其对 IS 损伤的内皮细胞的影响尚不清楚。本研究旨在探索在尿毒症模拟环境中外源性补充高密度脂蛋白对血管内皮细胞的影响。研究采用管形成、迁移、粘附和衰老试验来评估人主动脉内皮细胞(HAECs)的细胞功能。使用 Amplex red 试验测定了活性氧的生成。L-NAME 和 MCI186 分别用作一氧化氮合酶抑制剂和自由基清除剂。HDL通过激活HIF-1α/HO-1和抑制IL-1β/TNF-α/IL-6在IS刺激的HAECs中发挥抗炎和抗氧化作用。HDL 通过上调 IS 刺激 HAECs 的 Akt/eNOS/VEGF/SDF-1,改善血管生成能力。HDL 通过下调 VCAM-1 和 ICAM-1 降低了 IS 刺激的 HAEC 的内皮粘附性。此外,在 IS 刺激的 HAECs 中,HDL 通过上调 SIRT1 和下调 p53 减少了细胞衰老。重要的是,HDL的上述有益作用主要是由于其抗氧化能力。总之,HDL通过其抗氧化能力对血管内皮细胞产生了全面的保护作用,使其免受IS的损伤。本研究结果可为有内皮损伤的慢性肾脏病患者补充高密度脂蛋白提供理论依据。
High-density lipoprotein protects vascular endothelial cells from indoxyl sulfate insults through its antioxidant ability.
Chronic kidney disease (CKD) patients have a high risk of cardiovascular disease. Indoxyl sulfate (IS) is a uremic toxin that has been shown to inhibit nitric oxide production and cause cell senescence by inducing oxidative stress. High-density lipoprotein (HDL) has a protective effect on the cardiovascular system; however, its impacts on IS-damaged endothelial cells are still unknown. This study aimed to explore the effects of exogenous supplement of HDL on vascular endothelial cells in a uremia-mimic environment. Tube formation, migration, adhesion, and senescence assays were used to evaluate the cell function of human aortic endothelial cells (HAECs). Reactive oxygen species generation was measured by using Amplex red assay. L-NAME and MCI186 were used as a nitric oxide synthase inhibitor and a free radical scavenger, respectively. HDL exerted anti-inflammatory and antioxidant effects via HIF-1α/HO-1 activation and IL-1β/TNF-α/IL-6 inhibition in IS-stimulated HAECs. HDL improved angiogenesis ability through upregulating Akt/eNOS/VEGF/SDF-1 in IS-stimulated HAECs. HDL decreased endothelial adhesiveness via downregulating VCAM-1 and ICAM-1 in IS-stimulated HAECs. Furthermore, HDL reduced cellular senescence via upregulating SIRT1 and downregulating p53 in IS-stimulated HAECs. Importantly, the above beneficial effects of HDL were mainly due to its antioxidant ability. In conclusion, HDL exerted a comprehensive protective effect on vascular endothelial cells against damage from IS through its antioxidant ability. The results of this study might provide a theoretical basis for potential HDL supplementation in CKD patients with endothelial damage.
期刊介绍:
Cell Cycle is a bi-weekly peer-reviewed journal of high priority research from all areas of cell biology. Cell Cycle covers all topics from yeast to man, from DNA to function, from development to aging, from stem cells to cell senescence, from metabolism to cell death, from cancer to neurobiology, from molecular biology to therapeutics. Our goal is fast publication of outstanding research.