Apolipoprotein A-I mimetic peptide reverses impaired arterial healing after injury by reducing oxidative stress.
Apolipoprotein A-I mimetic peptide reverses impaired arterial healing after injury by reducing oxidative stress.
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DOI：
10.1016/j.atherosclerosis.2015.06.018
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发表时间：
2015-08
期刊：
影响因子：
5.3
通讯作者：
Graham LM
中科院分区：
文献类型：
--
作者：
Rosenbaum MA;Chaudhuri P;Abelson B;Cross BN;Graham LM
血管内皮细胞(EC)迁移对于血管成形术引起的动脉损伤的修复至关重要，但高胆固醇饮食抑制了内皮修复。体内研究表明，载脂蛋白A-I(apoA-I)是高密度脂蛋白的主要蛋白质成分，对于动脉损伤的正常愈合是必不可少的。ApoA-I模拟物，包括4F，已经被设计来模拟apoA-I分子的两亲性部分。这项研究是为了确定4F是否能促进内皮细胞的迁移和愈合。采用刮刀刮片法检测4F对EC体外迁移的影响。在小鼠颈动脉电损伤后评估体内内皮细胞的愈合。氧化应激的标记物也被检测。脂质氧化产物在体外可抑制EC的迁移，但与L-4F预先孵育可抑制EC的迁移。高胆固醇饮食的小鼠颈动脉损伤的内皮愈合比饮食饮食的小鼠延迟，在5天时分别为27.8%和48.2%。给予D-4F可将高胆固醇饮食小鼠的内皮愈合率提高到43.4%。D-4F给药对血脂水平无影响，但可降低氧化标志物。在体内，内皮修复和血浆氧化应激标志物之间存在显著的负相关。这些研究表明，apoA-I模拟物可以通过减少氧化应激来促进动脉损伤的内皮修复。
Endothelial cell (EC) migration is essential for healing of arterial injuries caused by angioplasty, but a high cholesterol diet inhibits endothelial repair. In vivo studies suggest that apolipoprotein A-I (apoA-I), the major protein constituent of HDL, is essential for normal healing of arterial injuries. ApoA-I mimetics, including 4F, have been designed to mimic the amphipathic portion of the apoA-I molecule. This study was undertaken to determine if 4F improves endothelial migration and healing. A razor scrape assay was used to analyze the effect of 4F on EC migration in vitro. Endothelial healing in vivo was assessed following electrical injury of carotid arteries in mice. Markers of oxidative stress were also examined. Lipid oxidation products inhibited EC migration in vitro, but preincubation with L-4F preserved EC migration. Endothelial healing of carotid arterial injuries in mice on a high cholesterol diet was delayed compared with mice on a chow diet with 27.8% vs. 48.2% healing, respectively, at 5 days. Administration of D-4F improved endothelial healing in mice on a high cholesterol diet to 43.4%. D-4F administration had no effect on lipid levels but decreased markers of oxidation. In vivo, there was a significant inverse correlation between endothelial healing and plasma markers of oxidative stress. These studies suggested that an apoA-I mimetic can improve endothelial healing of arterial injuries by decreasing oxidative stress.