Human C-reactive protein induces endothelial dysfunction and uncoupling of eNOS in vivo.
Human C-reactive protein induces endothelial dysfunction and uncoupling of eNOS in vivo.
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DOI：
10.1016/j.atherosclerosis.2009.02.002
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发表时间：
2009-09
期刊：
影响因子：
5.3
通讯作者：
Jialal, Ishwarlal
中科院分区：
文献类型：
--
作者：
Hein, Travis W.;Singh, Uma;Vasquez-Vivar, Jeannette;Devaraj, Sridevi;Kuo, Lih;Jialal, Ishwarlal
c反应蛋白（CRP）水平升高与心血管事件和内皮功能障碍增加有关。我们之前的研究表明，CRP降低内皮细胞中内皮型一氧化氮合酶（eNOS）的活性，并抑制内皮依赖性一氧化氮（NO）介导的体外血管舒张。在此，我们在一个有效的动物模型中研究了体内给药CRP对内皮功能的影响及其潜在机制。Sprague-Dawley大鼠每天腹腔注射20 mg/kg体重的人CRP或人血清白蛋白（HuSA），连续3天。第4天，分离肠系膜小动脉并加压进行血管舒缩研究，并对主动脉组织进行生化和分子分析。经CRP治疗后，肠系膜小动脉对乙酰胆碱而非硝普钠的扩张明显减少。与husa处理的大鼠相比，crp处理的主动脉组织匀浆中eNOS活性、eNOS二聚体/单体比、四氢生物蝶素水平和GTPCH1蛋白表达显著降低。CRP治疗还导致主动脉内皮超氧化物双氢乙啶染色增加和NADPH氧化酶调节亚基p47phox的膜易位。我们的数据为CRP在体内通过损害eNOS依赖性血管舒张和eNOS解偶联的有害作用提供了新的证据。
Elevated C-reactive protein (CRP) levels are associated with increased cardiovascular events and endothelial dysfunction. We have previously shown that CRP decreases endothelial nitric oxide synthase (eNOS) activity in endothelial cells and inhibits endothelium-dependent nitric oxide (NO)-mediated vasodilation in-vitro. Herein, we examined the effect of in-vivo administration of CRP on endothelial function and underlying mechanisms in a valid animal model. Sprague-Dawley rats were injected intraperitoneally daily for 3 days with human CRP or human serum albumin (HuSA) at 20 mg/kg body weight. On day 4, mesenteric arterioles were isolated and pressurized for vasomotor study and aortic tissue was subjected to biochemical and molecular analysis. Dilation of mesenteric arterioles to acetylcholine but not to sodium nitroprusside was significantly reduced following CRP treatment. The eNOS activity, eNOS dimer/monomer ratio, tetrahydrobiopterin levels, and protein expression of GTPCH1 were significantly lower in aortic tissue homogenates from CRP-treated than HuSA-treated rats. CRP treatment also resulted in increased dihydroethidium staining for superoxide in aortic endothelium and membrane translocation of p47phox, a regulatory subunit of NADPH oxidase. Our data provide novel evidence for the detrimental action of CRP in vivo by impairing eNOS-dependent vasodilation and uncoupling of eNOS.
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影响因子：
6
作者：
Cleland, SJ;Sattar, N;Connell, JMC
通讯作者：
Connell, JMC
影响因子：
15.9
作者：
Landmesser, U;Dikalov, S;Harrison, DG
通讯作者：
Harrison, DG
影响因子：
3
作者：
Maier, W;Cosentino, F;Lüscher, TF
通讯作者：
Lüscher, TF
DOI：
10.1161/01.atv.0000159890.10526.1e
发表时间：
2005-05-01
影响因子：
8.7
作者：
Qamirani, E;Ren, Y;Hein, TW
通讯作者：
Hein, TW
影响因子：
--
作者：
KUO, L;CHILIAN, WM;DAVIS, MJ
通讯作者：
DAVIS, MJ