Thioredoxin reverses age-related hypertension by chronically improving vascular redox and restoring eNOS function.
Thioredoxin reverses age-related hypertension by chronically improving vascular redox and restoring eNOS function.
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DOI：
10.1126/scitranslmed.aaf6094
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发表时间：
2017-02-08
影响因子：
17.1
通讯作者：
Das KC
中科院分区：
文献类型：
--
作者：
Hilgers RH;Kundumani-Sridharan V;Subramani J;Chen LC;Cuello LG;Rusch NJ;Das KC
随着年龄的增长，高血压的发病率显著增高，是多种心血管疾病发生或进展的独立预后因素。虽然与年龄有关的高血压是一种既定的现象，但目前的治疗只能缓解而不能治愈。因此，迫切需要一种治疗老年性高血压的方法，这可以大大降低心血管疾病的发病率。我们发现，在小鼠中过度表达人类硫氧还蛋白（TRX），一种氧化还原蛋白，可以预防与年龄相关的高血压。此外，连续三天注射重组人TRX （rhTRX）可以逆转老年野生型小鼠的高血压，这种效果持续至少20天。与注射盐水的老龄野生型小鼠或TRX缺乏小鼠相比，注射rhTRX的野生型小鼠或TRX过表达小鼠的动脉硬化程度降低，内皮依赖性松弛增强，一氧化氮生成增加，超氧阴离子（O2•−）生成减少。我们的研究表明rhTRX在逆转年龄相关性高血压方面具有潜在的翻译作用，并且具有持久的疗效。
The incidence of high blood pressure with advancing age is notably high, and it is an independent prognostic factor for the onset or progression of a variety of cardiovascular disorders. Although age-related hypertension is an established phenomenon, current treatments are only palliative but not curative. Thus, there is a critical need for a curative therapy against age-related hypertension, which could greatly decrease the incidence of cardiovascular disorders. We show that overexpression of human thioredoxin (TRX), a redox protein, in mice prevents age-related hypertension. Further, injection of recombinant human TRX (rhTRX) for three consecutive days reversed hypertension in aged wild-type mice, and this effect lasted for at least 20 days. Arteries of wild-type mice injected with rhTRX or mice with TRX overexpression exhibited decreased arterial stiffness, greater endothelium-dependent relaxation, increased nitric oxide production, and decreased superoxide anion (O2•−) generation compared to either saline-injected aged wild-type mice or mice with TRX deficiency. Our study demonstrates a potential translational role of rhTRX in reversing age-related hypertension with long-lasting efficacy.
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DOI：
10.1074/jbc.m112.415992
发表时间：
2013-01-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Crabtree MJ;Brixey R;Batchelor H;Hale AB;Channon KM
通讯作者：
Channon KM
影响因子：
64.8
作者：
Chen, Chun-An;Wang, Tse-Yao;Varadharaj, Saradhadevi;Reyes, Levy A.;Hemann, Craig;Talukder, M. A. Hassan;Chen, Yeong-Renn;Druhan, Lawrence J.;Zweier, Jay L.
通讯作者：
Zweier, Jay L.
影响因子：
8.3
作者：
Hamilton, CA;Brosnan, MJ;Dominiczak, AF
通讯作者：
Dominiczak, AF
DOI：
10.1152/ajplung.00285.2014
发表时间：
2015-03-01
影响因子：
4.9
作者：
Das, Kumuda C.
通讯作者：
Das, Kumuda C.
Mkk4 是与心房重塑和心律失常发生相关的转化生长因子 Beta 1 信号传导的负调节因子
影响因子：
5.4
作者：
Davies L;Jin J;Shen W;Tsui H;Shi Y;Wang Y;Zhang Y;Hao G;Wu J;Chen S;Fraser JA;Dong N;Christoffels V;Ravens U;Huang CL;Zhang H;Cartwright EJ;Wang X;Lei M
通讯作者：
Lei M