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首页> 外文期刊>Redox Biology >Apolipoprotein A-1 mimetic peptide 4F promotes endothelial repairing and compromises reendothelialization impaired by oxidized HDL through SR-B1
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Apolipoprotein A-1 mimetic peptide 4F promotes endothelial repairing and compromises reendothelialization impaired by oxidized HDL through SR-B1

机译:载脂蛋白A-1模拟肽4F促进内皮修复并损害被SR-B1氧化的HDL损伤的内皮再形成

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Disruption of endothelial monolayer integrity is the primary instigating factor for many cardiovascular diseases. High density lipoprotein (HDL) oxidized by heme enzyme myeloperoxidase (MPO) is dysfunctional in promoting endothelial repair. Apolipoprotein A-1 mimetic 4F with its pleiotropic benefits has been proven effective in many in vivo models. In this study we investigated whether 4F promotes endothelial repair and restores the impaired function of oxidized HDL (Cl/NO2-HDL) in promoting re-endothelialization. We demonstrate that 4F and Cl/NO2-HDL act on scavenger receptor type I (SR-B1) using human aorta endothelial cells (HAEC) and SR-B1 (-/-) mouse aortic endothelial cells. Wound healing, transwell migration, lamellipodia formation and single cell migration assay experiments show that 4F treatment is associated with a recovery of endothelial cell migration and associated with significantly increased endothelial nitric oxide synthase (eNOS) activity, Akt phosphorylation and SR-B1 expression. 4F increases NO generation and diminishes oxidative stress. In vivo , 4F can stimulate cell proliferation and re-endothelialization in the carotid artery after treatment with Cl/NO2-HDL in a carotid artery electric injury model but fails to do so in SR-B1(-/-) mice. These findings demonstrate that 4F promotes endothelial cell migration and has a potential therapeutic benefit against early endothelial injury in cardiovascular diseases.
机译:内皮单层完整性的破坏是许多心血管疾病的主要诱因。被血红素酶髓过氧化物酶(MPO)氧化的高密度脂蛋白(HDL)在促进内皮修复中功能失调。具有多效性的载脂蛋白A-1模拟物4F已在许多体内模型中被证明是有效的。在这项研究中,我们研究了4F是否促进内皮修复并恢复氧化HDL(Cl / NO 2 -HDL)促进内皮再血管化的功能受损。我们证明了4F和Cl / NO 2 -HDL使用人主动脉内皮细胞(HAEC)和SR-B1 (-/-)<对清除剂受体I(SR-B1)起作用/ sup>小鼠主动脉内皮细胞。伤口愈合,跨孔迁移,片状脂蛋白形成和单细胞迁移实验表明,4F治疗与内皮细胞迁移的恢复有关,并且与内皮一氧化氮合酶(eNOS)活性,Akt磷酸化和SR-B1表达的显着增加有关。 4F增加NO生成并减少氧化应激。在体内,4F可以在颈动脉电损伤模型中用Cl / NO 2 -HDL治疗后刺激颈动脉中的细胞增殖和再内皮化,但在SR-B1 (-/-)小鼠。这些发现表明4F促进内皮细胞迁移,并且对于心血管疾病中的早期内皮损伤具有潜在的治疗益处。

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