Abstract P215: Role of Nox4 - H 2 O 2 Production in Cctivation of mTORC1 in Salt-Induced Hypertension and Kidney Injury in Dahl S Rats

Hypertension ◽  
2018 ◽  
Vol 72 (Suppl_1) ◽  
Author(s):  
Vikash Kumar ◽  
Theresa Kurth ◽  
Allen Cowley
Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Wei Wang ◽  
Roxanna A Irani ◽  
Haixiong Liu ◽  
Yujing Zhang ◽  
Lijian Tao ◽  
...  

Preeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy that is a leading cause of maternal and neonatal mortality and morbidity. The current treatment for PE is limited because underlying pathophysiologic mechanisms remain undefined. PE is, however, recognized as an autoimmune disease, which is associated with a series of inflammatory cytokines. Using sensitive ELISA arrays, we discovered a pronounced inflammatory response was stimulated in circulation of PE patients, including elevated levels of LIGHT, a novel TNF superfamily member, which is involved in pathogenesis of series of autoimmune diseases. Next, we confirmed that LIGHT is significantly increased in the circulation and placenta women with PE. In order to determine the role of LIGHT in pathophyisology of PE, we injected recombinant LIGHT into pregnant mice and non-pregnant mice. We demonstrated that LIGHT directly induces major clinical PE features including hypertension (161±3mmHg vs. control 122±3mmHg, p<0.05) and proteinuria (57±2.7μg/mg vs. control 22±2.5μg albumin/mg creatinine, p<0.05) in the pregnant mice. In contrast,LIGHT only induced hypertension (149±2mmHg vs. control 122±8mmHg, p<0.05) but not proteinuria in non-pregnant mice, indicating LIGHT has a previously unrecognized role in pathophysiology of PE and its detrimental effects on kidney injury is pregnancy-dependent. Mechanistically, using neutralizing antibodies for LIGHT receptors, we found that LIGHT transmembrane receptors, HVEM and LTβR, are required for LIGHT-induced hypertension and proteinuria in the pregnant mice by inducing sFlt-1 production, impaired placental angiogenesis and endothelium dysfunction in pregnant mice. Overall, our studies provide both human and mouse evidence that elevated LIGHT contributes to pathophysiology of PE via both HVEM and LTβR signaling and immediately suggest a novel therapeutic possibility.


2014 ◽  
Vol 38 (5) ◽  
pp. S62
Author(s):  
Shiao-Ying Chang ◽  
Chao-Sheng Lo ◽  
Xin-Ping Zhao ◽  
Yessoufou Aliou ◽  
Isabelle Chenier ◽  
...  

2015 ◽  
Vol 4 (3) ◽  
pp. 205 ◽  
Author(s):  
Shikha Saxena ◽  
KV Thimmaraju ◽  
PremC Srivastava ◽  
AyazK Mallick ◽  
Biswajit Das ◽  
...  

2013 ◽  
Vol 14 (4) ◽  
pp. 275-281 ◽  
Author(s):  
Shingo Takatori ◽  
Yoshito Zamami ◽  
Narumi Hashikawa-Hobara ◽  
Hiromu Kawasaki

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