排序方式: 共有46条查询结果,搜索用时 31 毫秒
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Annet Kirabo Vanessa Fontana Ana P.C. de Faria Roxana Loperena Cristi L. Galindo Jing Wu Alfiya T. Bikineyeva Sergey Dikalov Liang Xiao Wei Chen Mohamed A. Saleh Daniel W. Trott Hana A. Itani Antony Vinh Venkataraman Amarnath Kalyani Amarnath Tomasz J. Guzik Kenneth E. Bernstein Xiao Z. Shen Yu Shyr Sheau-chiann Chen Raymond L. Mernaugh Cheryl L. Laffer Fernando Elijovich Sean S. Davies Heitor Moreno Meena S. Madhur Jackson Roberts II David G. Harrison 《The Journal of clinical investigation》2014,124(10):4642-4656
Oxidative damage and inflammation are both implicated in the genesis of
hypertension; however, the mechanisms by which these stimuli promote
hypertension are not fully understood. Here, we have described a pathway in
which hypertensive stimuli promote dendritic cell (DC) activation of T cells,
ultimately leading to hypertension. Using multiple murine models of
hypertension, we determined that proteins oxidatively modified by highly
reactive γ-ketoaldehydes (isoketals) are formed in hypertension and
accumulate in DCs. Isoketal accumulation was associated with DC production of
IL-6, IL-1β, and IL-23 and an increase in costimulatory proteins CD80 and
CD86. These activated DCs promoted T cell, particularly CD8+ T cell,
proliferation; production of IFN-γ and IL-17A; and hypertension. Moreover,
isoketal scavengers prevented these hypertension-associated events. Plasma
F2-isoprostanes, which are formed in concert with isoketals, were found to be
elevated in humans with treated hypertension and were markedly elevated in
patients with resistant hypertension. Isoketal-modified proteins were also
markedly elevated in circulating monocytes and DCs from humans with
hypertension. Our data reveal that hypertension activates DCs, in large part by
promoting the formation of isoketals, and suggest that reducing isoketals has
potential as a treatment strategy for this disease. 相似文献
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Dees C Akhmetshina A Zerr P Reich N Palumbo K Horn A Jüngel A Beyer C Krönke G Zwerina J Reiter R Alenina N Maroteaux L Gay S Schett G Distler O Distler JH 《The Journal of experimental medicine》2011,208(5):961-972
Vascular damage and platelet activation are associated with tissue remodeling in diseases such as systemic sclerosis, but the molecular mechanisms underlying this association have not been identified. In this study, we show that serotonin (5-hydroxytryptamine [5-HT]) stored in platelets strongly induces extracellular matrix synthesis in interstitial fibroblasts via activation of 5-HT(2B) receptors (5-HT(2B)) in a transforming growth factor β (TGF-β)-dependent manner. Dermal fibrosis was reduced in 5-HT(2B)(-/-) mice using both inducible and genetic models of fibrosis. Pharmacologic inactivation of 5-HT(2B) also effectively prevented the onset of experimental fibrosis and ameliorated established fibrosis. Moreover, inhibition of platelet activation prevented fibrosis in different models of skin fibrosis. Consistently, mice deficient for TPH1, the rate-limiting enzyme for 5-HT production outside the central nervous system, showed reduced experimental skin fibrosis. These findings suggest that 5-HT/5-HT(2B) signaling links vascular damage and platelet activation to tissue remodeling and identify 5-HT(2B) as a novel therapeutic target to treat fibrotic diseases. 相似文献
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Curaxins: anticancer compounds that simultaneously suppress NF-κB and activate p53 by targeting FACT
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