Monoamine Oxidases Are Mediators of Endothelial Dysfunction in the Mouse Aorta
Monoamine Oxidases Are Mediators of Endothelial Dysfunction in the Mouse Aorta
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单胺氧化酶是小鼠主动脉内皮功能障碍的介质
DOI：
10.1161/hypertensionaha.113.01314
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发表时间：
2013
期刊：
影响因子：
8.3
通讯作者：
Brandes RP
中科院分区：
文献类型：
--
作者：
Sturza A;Leisegang M;Babelova A;Schröder K;Benkhoff S;Loot AE;Fleming I;Schulz R;Muntean D;Brandes RP
单胺氧化酶（MAO）产生H2 O2作为其催化循环的副产物。MAO是否是内皮功能障碍的介质尚不清楚，并且在血管紧张素II和脂多糖小鼠血管功能障碍模型中确定。实时定量聚合酶链反应显示，小鼠睾丸含有参与儿茶酚胺生成的酶和MAO-A和MAO-B mRNA。Western blot检测到MAO-A和-B蛋白在小鼠血管内皮细胞和人脐静脉内皮细胞中均有表达。体外培养小鼠主动脉与重组单胺氧化酶-A增加过氧化氢的形成和诱导内皮功能障碍，这是减弱聚乙二醇-过氧化氢酶和单胺氧化酶抑制剂。体内脂多糖（8 mg/kg IP过夜）或血管紧张素II（1 mg/kg/天，2周，微型泵）治疗诱导血管MAO-A和-B表达，并导致响应乙酰胆碱的主动脉内皮依赖性舒张减弱。MAO抑制剂使脂多糖和血管紧张素II诱导的主动脉活性氧簇形成减少了50%（亚铁氧化二甲酚橙子测定），并使内皮依赖性舒张部分正常化。单胺氧化酶-A和单胺氧化酶-B抑制剂有相加作用;联合应用完全恢复内皮依赖性舒张。为了确定MAO依赖性H2 O2形成如何诱导内皮功能障碍，测定了环GMP。组胺刺激人脐静脉内皮细胞激活内皮NO合酶导致环GMP的增加，这几乎被废除的单胺氧化酶-A曝光。MAO抑制阻止了这种作用，表明MAO诱导的H2 O2形成足以减弱内皮NO释放。因此，MAO-A和MAO-B都在小鼠主动脉中表达，由体内脂多糖和血管紧张素II处理诱导，并通过产生H2 O2促进血管疾病模型中的内皮功能障碍。
Monoamine oxidases (MAOs) generate H2O2as a by-product of their catalytic cycle. Whether MAOs are mediators of endothelial dysfunction is unknown and was determined here in the angiotensin II and lipopolysaccharide-models of vascular dysfunction in mice. Quantitative real-time polymerase chain reaction revealed that mouse aortas contain enzymes involved in catecholamine generation and MAO-A and MAO-B mRNA. MAO-A and -B proteins could be detected by Western blot not only in mouse aortas but also in human umbilical vein endothelial cells. Ex vivo incubation of mouse aorta with recombinant MAO-A increased H2O2formation and induced endothelial dysfunction that was attenuated by polyethylene glycol-catalase and MAO inhibitors. In vivo lipopolysaccharide (8 mg/kg IP overnight) or angiotensin II (1 mg/kg per day, 2 weeks, minipump) treatment induced vascular MAO-A and -B expressions and resulted in attenuated endothelium-dependent relaxation of the aorta in response to acetylcholine. MAO inhibitors reduced the lipopolysaccharide- and angiotensin II–induced aortic reactive oxygen species formation by 50% (ferrous oxidation xylenol orange assay) and partially normalized endothelium-dependent relaxation. MAO-A and MAO-B inhibitors had an additive effect; combined application completely restored endothelium-dependent relaxation. To determine how MAO-dependent H2O2formation induces endothelial dysfunction, cyclic GMP was measured. Histamine stimulation of human umbilical vein endothelial cells to activate endothelial NO synthase resulted in an increase in cyclic GMP, which was almost abrogated by MAO-A exposure. MAO inhibition prevented this effect, suggesting that MAO-induced H2O2formation is sufficient to attenuate endothelial NO release. Thus, MAO-A and MAO-B are both expressed in the mouse aorta, induced by in vivo lipopolysaccharide and angiotensin II treatment and contribute via the generation of H2O2to endothelial dysfunction in vascular disease models.
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血管紧张素 II 可以增加神经元培养物中去甲肾上腺素的代谢。
DOI：
10.1152/ajpcell.1987.252.6.c650
发表时间：
1987
期刊：
The American journal of physiology
影响因子：
--
作者：
Sumners,C;Shalit,SL;Kalberg,CJ;Raizada,MK
通讯作者：
Raizada,MK
影响因子：
5.8
作者：
M. Youdim;J. Finberg
通讯作者：
M. Youdim;J. Finberg
DOI：
10.1164/ajrccm.160.2.9810073
发表时间：
1999-08-01
影响因子：
24.7
作者：
Annane, D;Trabold, F;Gajdos, P
通讯作者：
Gajdos, P
DOI：
10.1084/jem.20090449
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Loot AE;Schreiber JG;Fisslthaler B;Fleming I
通讯作者：
Fleming I
影响因子：
56.9
作者：
Burgoyne, Joseph R.;Madhani, Melanie;Eaton, Philip
通讯作者：
Eaton, Philip