Peroxynitrite mediates diabetes-induced endothelial dysfunction: possible role of Rho kinase activation.
Peroxynitrite mediates diabetes-induced endothelial dysfunction: possible role of Rho kinase activation.
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DOI：
10.1155/2010/247861
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发表时间：
2010
影响因子：
--
通讯作者：
Caldwell RW
中科院分区：
文献类型：
--
作者：
El-Remessy AB;Tawfik HE;Matragoon S;Pillai B;Caldwell RB;Caldwell RW
内皮功能障碍的特征在于由于其失活形成过氧亚硝酸盐或eNOS表达减少而导致NO的生物利用度降低。在这里，我们研究的因果作用过氧亚硝酸盐在介导糖尿病引起的内皮功能障碍。通过STZ注射诱导糖尿病，大鼠接受过氧亚硝酸盐分解催化剂（FeTTPs，15 mg/Kg/天）4周。血管舒张乙酰胆碱，氧化应激标志物，RhoA活性，和eNOS表达进行了测定。与对照组相比，糖尿病患者的冠状动脉ACh介导的最大舒张功能显著降低。糖尿病血管也显示脂质过氧化物，硝基酪氨酸和活性RhoA显着增加，eNOS mRNA表达减少50%。用FeTTPS治疗糖尿病动物阻断了这些作用。在主动脉内皮细胞中的研究表明，高糖或过氧亚硝酸盐增加活性RhoA激酶水平，降低eNOS表达和NO水平，这与阻断过氧亚硝酸盐或Rho激酶逆转。总之，过氧亚硝酸盐可以通过激活RhoA抑制eNOS表达，从而引起血管功能障碍。
Endothelial dysfunction is characterized by reduced bioavailability of NO due to its inactivation to form peroxynitrite or reduced expression of eNOS. Here, we examine the causal role of peroxynitrite in mediating diabetes-induced endothelial dysfunction. Diabetes was induced by STZ-injection, and rats received the peroxynitrite decomposition catalyst (FeTTPs, 15 mg/Kg/day) for 4 weeks. Vasorelaxation to acetylcholine, oxidative-stress markers, RhoA activity, and eNOS expression were determined. Diabetic coronary arteries showed significant reduction in ACh-mediated maximal relaxation compared to controls. Diabetic vessels showed also significant increases in lipid-peroxides, nitrotyrosine, and active RhoA and 50% reduction in eNOS mRNA expression. Treatment of diabetic animals with FeTTPS blocked these effects. Studies in aortic endothelial cells show that high glucose or peroxynitrite increases the active RhoA kinase levels and decreases eNOS expression and NO levels, which were reversed with blocking peroxynitrite or Rho kinase. Together, peroxynitrite can suppress eNOS expression via activation of RhoA and hence cause vascular dysfunction.
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DOI：
10.1124/jpet.109.157941
发表时间：
2010-01-01
影响因子：
3.5
作者：
Abdelsaid, Mohammed A.;Pillai, Bindu A.;El-Remessy, Azza B.
通讯作者：
El-Remessy, Azza B.
影响因子：
4.8
作者：
El-Remessy, A. B.;Al-Shabrawey, M.;Caldwell, R. B.
通讯作者：
Caldwell, R. B.
DOI：
10.1152/ajpheart.00761.2007
发表时间：
2007-12-01
影响因子：
4.8
作者：
Quijano, Celia;Castro, Laura;Radi, Rafael
通讯作者：
Radi, Rafael
影响因子：
2
作者：
Kamata, K;Kobayashi, T;Sugiura, M
通讯作者：
Sugiura, M
影响因子：
7.4
作者：
Pieper, GM;Siebeneich, W;Del Soldato, P
通讯作者：
Del Soldato, P