Effect of aging, MnSOD deficiency, and genetic background on endothelial function evidence for MnSOD haploinsufficiency
Effect of aging, MnSOD deficiency, and genetic background on endothelial function evidence for MnSOD haploinsufficiency
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DOI：
10.1161/atvbaha.107.146852
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发表时间：
2007-09-01
影响因子：
8.7
通讯作者：
Faraci, Frank M.
中科院分区：
文献类型：
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作者：
Brown, Kathryn A.;Didion, Sean P.;Faraci, Frank M.
目的-本研究的目的是比较血管功能，超氧化物水平，和MnSOD蛋白表达（4至7个月）及以上（22至24个月）MnSOD+/+和MnSOD缺乏（MnSOD+/-）小鼠。方法和结果-在离体主动脉对内皮依赖性扩张剂乙酰胆碱（ACh）的舒张作用在年轻的MnSOD+/+（n = 9）和年轻的MnSOD+/-（n = 6）。这种反应在年老的MnSOD+/+（n = 8）小鼠和年老的MnSOD+/-小鼠（n = 14）中受损，在年老的MnSOD缺陷小鼠中功能障碍更严重（例如，100 μ mol/L ACh在年轻MnSOD+/+、年轻MnSOD+/-、老年MnSOD +/+、和老年MnSOD+/-小鼠）。在C57 BL/6和CD-1遗传背景的小鼠中，内皮功能障碍相似。与ACh相比，MnSOD+/+和MnSOD+/-小鼠对内皮非依赖性扩张剂硝普钠的反应增强（P < 0.05）。用光泽精增强化学发光法测得，老年MnSOD+/-小鼠的超氧化物水平比老年MnSOD+/+和年轻小鼠增加2倍以上（P < 0.05）。结论-这些数据提供了第一个直接证据，即MnSOD halpoinsufficiency导致血管氧化应激增加和内皮功能障碍。
Objective - The goal of this study was to compare vascular function, superoxide levels, and MnSOD protein expression in young (4 to 7 months) and old (22 to 24 months) MnSOD+/+ and MnSOD-deficient (MnSOD+/-) mice.Methods and Results - Relaxation of aorta in vitro to the endothelium-dependent dilator acetylcholine (ACh) was similar in young MnSOD+/+ (n = 9) and young MnSOD+/- (n = 6) mice. This response was impaired in old MnSOD+/+ (n = 8) mice and old MnSOD+/- mice (n = 14), with dysfunction being greater in old MnSOD-deficient mice (eg, 100 mu mol/L ACh produced 77 +/- 3% [mean +/- SE], 77 +/- 3%, 70 +/- 4%, and 57 +/- 4% relaxation in young MnSOD+/+, young MnSOD+/-, old MnSOD+/+, and old MnSOD+/- mice, respectively). The endothelial dysfunction was similar in mice on both C57BL/6 and CD-1 genetic backgrounds. In contrast to ACh, responses to the endothelium-independent dilator sodium nitroprusside were enhanced in old MnSOD+/+ and MnSOD+/- mice compared with both groups of young mice (P < 0.05). Superoxide levels, as measured using lucigenin-enhanced chemiluminescence, were increased more than 2-fold in old MnSOD+/- mice compared with old MnSOD+/+ and young mice (P < 0.05).Conclusions - These data provide the first direct evidence that MnSOD halpoinsufficiency results in increased vascular oxidative stress and endothelial dysfunction with aging.