Apolipoprotein A-1 mimetic peptide 4F promotes endothelial repairing and compromises reendothelialization impaired by oxidized HDL through SR-B1.
Apolipoprotein A-1 mimetic peptide 4F promotes endothelial repairing and compromises reendothelialization impaired by oxidized HDL through SR-B1.
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载脂蛋白 A-1 模拟肽 4F 通过 SR-B1 促进内皮修复并损害因氧化 HDL 受损的再内皮化
DOI：
10.1016/j.redox.2017.11.027
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发表时间：
2018-05
期刊：
影响因子：
11.4
通讯作者：
Zheng L
中科院分区：
文献类型：
--
作者：
He D;Zhao M;Wu C;Zhang W;Niu C;Yu B;Jin J;Ji L;Willard B;Mathew AV;Chen YE;Pennathur S;Yin H;He Y;Pan B;Zheng L
内皮细胞单层完整性的破坏是许多心血管疾病的主要诱发因素。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。载脂蛋白A-1模拟物4F具有多效性益处，已被证明在许多体内模型中有效。在这项研究中，我们研究了4F是否促进内皮修复和恢复受损的功能，氧化HDL（Cl/NO2-HDL）在促进再内皮化。我们用人主动脉内皮细胞（HAEC）和SR-B1（-/-）小鼠主动脉内皮细胞证明了4F和Cl/NO2-HDL作用于清道夫受体I型（SR-B1）。伤口愈合、transwell迁移、板状伪足形成和单细胞迁移试验表明，4F处理与内皮细胞迁移的恢复相关，并与显著增加的内皮一氧化氮合酶（eNOS）活性、Akt磷酸化和SR-B1表达相关。4F增加NO生成并减少氧化应激。在体内，4F可以刺激Cl/NO2-HDL处理后的颈动脉电损伤模型中的细胞增殖和再内皮化，但在SR-B1（-/-）小鼠中不能这样做。这些发现表明，4F促进内皮细胞迁移，并对心血管疾病中的早期内皮损伤具有潜在的治疗益处。4F可恢复Cl/NO2-HDL促进内皮修复的能力。4F增加NO生成并减少氧化应激。4F增加eNOS活性、Akt磷酸化和SR-B1表达。在颈动脉电损伤模型中，4F可以刺激再内皮化。
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. 4F restores the decreased ability of Cl/NO2-HDL in promoting endothelial repair. 4F increases NO generation and diminishes oxidative stress. 4F increases eNOS activity, Akt phosphorylation and SR-B1 expression. 4F can stimulate re-endothelialization in a carotid artery electric injury model.
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影响因子：
4.5
作者：
Getz GS;Reardon CA
通讯作者：
Reardon CA
DOI：
10.1253/circj.cj-11-0460
发表时间：
2011
期刊：
Circulation journal : official journal of the Japanese Circulation Society
影响因子：
--
作者：
Imaizumi S;Navab M;Morgantini C;Charles-Schoeman C;Su F;Gao F;Kwon M;Ganapathy E;Meriwether D;Farias-Eisner R;Fogelman AM;Reddy ST
通讯作者：
Reddy ST
影响因子：
4.3
作者：
Hall BA;Armitage JP;Sansom MS
通讯作者：
Sansom MS
影响因子：
6.5
作者：
Meriwether, David;Sulaiman, Dawoud;Reddy, Srinivasa T.
通讯作者：
Reddy, Srinivasa T.
影响因子：
15.9
作者：
Besler, Christian;Heinrich, Kathrin;Landmesser, Ulf
通讯作者：
Landmesser, Ulf