Antioxidant therapy reverses impaired graft healing in hypercholesterolemic rabbits.
Antioxidant therapy reverses impaired graft healing in hypercholesterolemic rabbits.
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DOI：
10.1016/j.jvs.2009.08.061
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发表时间：
2010-01
影响因子：
4.3
通讯作者：
Graham, Linda M.
中科院分区：
文献类型：
--
作者：
Rosenbaum, Michael A.;Miyazaki, Keiko;Colles, Scott M.;Graham, Linda M.
有限的内皮细胞（EC）覆盖和吻合口内膜增生有助于血栓形成和人工血管移植失败。脂质蓄积和脂质氧化与EC迁移减少和内膜增生相关。本研究的目的是评估抗氧化剂改善高胆固醇血症动物移植物愈合的能力。将家兔分为四组：饲料加N-乙酰半胱氨酸（NAC）、饲料加普罗布考、饲料加1%胆固醇加NAC或饲料加1%胆固醇加普罗布考。两周后，将12 cm长、4 mm内径的膨胀聚四氟乙烯移植物植入腹主动脉中。植入后6周，取出移植物并分析胆固醇含量、EC覆盖、吻合口内膜厚度和新生内膜的细胞组成。获得血浆样品以评估全身氧化应激。将该数据与先前报道的动物在饲料和含1%胆固醇饲料的饲料中的数据进行比较。与普通饲料喂养的家兔相比，喂养1%胆固醇饲料喂养的家兔的人工血管移植物吻合口内膜增厚明显更大，EC覆盖率更低。在高胆固醇血症兔中，抗氧化剂治疗降低了整体氧化应激，血浆硫代巴比妥酸反应物质减少了40%。在喂食1%胆固醇饲料的家兔中，NAC使近端吻合处的内膜增生减少了29%，并使移植物EC覆盖率从46%显著增加到71%（P = 0.03）。按照类似的模式，普罗布考减少内膜增生的43%，增加移植EC覆盖到53%的高胆固醇血症兔。在高胆固醇饮食的家兔中，整体氧化应激和吻合口内膜增生增加，人工血管移植物的内皮化显著减少。抗氧化剂治疗改善EC覆盖并减少内膜增生。减少氧化应激可促进假体移植物的愈合。在动物模型和人体中，高胆固醇血症与支架或静脉移植物置入后炎症反应增加、氧化应激升高和内膜增生增加相关。在高胆固醇血症动物中放置支架或移植物后观察到内皮化减少，并且在血清脂质水平升高的人中发现EC生长和EC接种移植物的通畅性减少。我们的研究结果表明，抗氧化剂是有效的，在减少这种病理反应和改善移植愈合。
Limited endothelial cell (EC) coverage and anastomotic intimal hyperplasia contribute to thrombosis and failure of prosthetic grafts. Lipid accumulation and lipid oxidation are associated with decreased EC migration and intimal hyperplasia. The goal of this study was to assess the ability of antioxidants to improve graft healing in hypercholesterolemic animals. Rabbits were placed in one of four groups: chow plus N-acetylcysteine (NAC), chow plus probucol, chow with 1% cholesterol plus NAC, or chow with 1% cholesterol plus probucol. After two weeks, 12 cm long, 4 mm internal diameter expanded polytetrafluoroethylene grafts were implanted in the abdominal aorta. Six weeks after implantation, the grafts were removed and analyzed for cholesterol content, EC coverage, anastomotic intimal thickness, and the cellular composition of the neointima. Plasma samples were obtained to assess systemic oxidative stress. The data was compared with previously reported data from animals on chow and chow with 1% cholesterol diets. Prosthetic grafts from rabbits on a chow with 1% cholesterol diet had significantly greater anastomotic intimal thickening and lower EC coverage than grafts from rabbits on a chow diet. In hypercholesterolemic rabbits, antioxidant therapy decreased global oxidative stress as evidenced by a 40% decrease in plasma thiobarbituric acid reactive substances. In rabbits on the chow with 1% cholesterol diet, NAC decreased intimal hyperplasia at the proximal anastomosis by 29% and significantly increased graft EC coverage from 46% to 71% (P = .03). Following a similar pattern, probucol decreased intimal hyperplasia by 43% and increased graft EC coverage to 53% in hypercholesterolemic rabbits. Global oxidative stress and anastomotic intimal hyperplasia are increased and endothelialization of prosthetic grafts is significantly reduced in rabbits on a high cholesterol diet. Antioxidant treatment improves EC coverage and decreases intimal hyperplasia. Reducing oxidative stress may promote healing of prosthetic grafts. Hypercholesterolemia is associated with an increased inflammatory response, elevated oxidative stress, and increased intimal hyperplasia following stent or vein graft placement in animal models and in humans. Reduced endothelialization is seen following stent or graft placement in hypercholesterolemic animals, and reduced EC growth and patency of EC-seeded grafts is found in humans with elevated serum lipid levels. Our results suggest that antioxidants are effective in reducing this pathologic response and improving graft healing.
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影响因子：
8.9
作者：
Geudens, Nele;De Wauwer, Caroline Van;Van Raemdonck, Dirk E. M.
通讯作者：
Van Raemdonck, Dirk E. M.
影响因子：
3.4
作者：
Miyauchi, K;Aikawa, M;Yamaguchi, H
通讯作者：
Yamaguchi, H
影响因子：
7.4
作者：
ARUOMA, OI;HALLIWELL, B;BUTLER, J
通讯作者：
BUTLER, J
影响因子：
8.7
作者：
JOHANSSON, J;OLSSON, AG;WALLDIUS, G
通讯作者：
WALLDIUS, G
DOI：
10.1161/01.atv.0000246777.30819.85
发表时间：
2006-12-01
影响因子：
8.7
作者：
Kappert, Kai;Sparwel, Jan;Ostman, Arne
通讯作者：
Ostman, Arne