Gene transfer of manganese superoxide dismutase reverses vascular dysfunction in the absence but not in the presence of atherosclerotic plaque
Gene transfer of manganese superoxide dismutase reverses vascular dysfunction in the absence but not in the presence of atherosclerotic plaque
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DOI：
10.1089/104303401750298562
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发表时间：
2001-07-01
影响因子：
4.2
通讯作者：
O'Brien, T
中科院分区：
文献类型：
--
作者：
Zanetti, M;Sato, J;O'Brien, T
在存在和不存在形态学异常的高胆固醇血症中观察到内皮依赖性血管舒张（EDVR）受损，可能是由于超氧阴离子。我们的目的是评估锰超氧化物歧化酶（MnSOD）的基因转移到血管的高胆固醇血症的动物和没有动脉粥样硬化斑块的影响，并比较内皮型一氧化氮合酶（eNOS）和MnSOD过表达对血管功能障碍的动脉粥样硬化的设置。家兔接受高胆固醇饮食10周，导致颈动脉中无斑块和主动脉中存在斑块的异常EDVR。在第1组中，将编码MnSOD（Ad MnSOD）或β-半乳糖苷酶（Ad β gal）的腺病毒载体递送至体内颈动脉。四天后，评估转基因表达和血管反应性。在第2组中，用AdMnSOD、AdeNOS或两者离体转导主动脉节段。24小时后评估转基因表达和血管反应性。在第1组中，MnSOD的表达检测到AdMnSOD transsided血管和受损的EDVR逆转的情况下动脉粥样硬化斑块。在第2组（存在动脉粥样硬化斑块），MnSOD和eNOS的表达检测Western分析，eNOS，但不是MnSOD过表达，改善EDVR，而eNOS和MnSOD同时过表达并不比eNOS单独。腺病毒介导的MnSOD基因转移到非动脉粥样硬化的颈动脉，而不是动脉粥样硬化的主动脉，正常化EDVR。eNOS基因转移改善EDVR，即使在斑块存在的情况下。
Impaired endothelium-dependent vasorelaxation (EDVR) is observed in hypercholesterolemia both in the presence and absence of morphological abnormalities and may be due to superoxide anions. Our aim was to assess the effect of gene transfer of manganese superoxide dismutase (MnSOD) to blood vessels from hypercholesterolemic animals with and without atherosclerotic plaque and to compare the effects of endothelial nitric oxide synthase (eNOS) and MnSOD over-expression on vascular dysfunction in the setting of atherosclerosis. Rabbits received a high-cholesterol diet for 10 weeks, resulting in abnormal EDVR in the absence of plaque in the carotids and the presence of plaque in the aorta. In Group 1, adenoviral vectors encoding MnSOD (Ad MnSOD) or beta -galactosidase (Ad beta gal) were delivered to the carotid arteries in vivo. Four days later, transgene expression and vascular reactivity were assessed. In Group 2, segments of the aorta were transduced ex vivo with AdMnSOD, AdeNOS or both. Transgene expression and vascular reactivity were assessed 24 hr later. In Group 1, MnSOD expression was detected in AdMnSOD-ransduced vessels and impaired EDVR was reversed in the absence of atherosclerotic plaque. In Group 2 (with atherosclerotic plaque present), MnSOD and eNOS expression were detected by western analysis, and eNOS, but not MnSOD over-expression, improved EDVR whereas simultaneous over-expression of eNOS and MnSOD was no better than eNOS alone. Adenovirus-mediated gene transfer of MnSOD to nonatherosclerotic carotid arteries, but not atherosclerotic aorta, normalizes EDVR. eNOS gene transfer improves EDVR, even in the presence of plaque.