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Vascular endothelial cell-specific NF-kappaB suppression attenuates hypertension-induced renal damage

Item Type:Article
Title:Vascular endothelial cell-specific NF-kappaB suppression attenuates hypertension-induced renal damage
Creators Name:Henke, N. and Schmidt-Ullrich, R. and Dechend, R. and Park, J.K. and Qadri, F. and Wellner, M. and Obst, M. and Gross, V. and Dietz, R. and Luft, F.C. and Scheidereit, C. and Mueller, D.N.
Abstract:Nuclear factor kappa B (NF-kappaB) participates in hypertension-induced vascular and target-organ damage. We tested whether or not endothelial cell-specific NF-kappaB suppression would be ameliorative. We generated Cre/lox transgenic mice with endothelial cell-restricted NF-kappaB super-repressor IkappaBalphaDeltaN (Tie-1-DeltaN mice) overexpression. We confirmed cell-specific IkappaBalphaDeltaN expression and reduced NF-kappaB activity after TNF-alpha stimulation in primary endothelial cell culture. To induce hypertension with target-organ damage, we fed mice a high-salt diet and N(omega)-nitro-L-arginine-methyl-ester (L-NAME) and infused angiotensin (Ang) II. This treatment caused a 40-mm Hg blood pressure increase in both Tie-1-DeltaN and control mice. In contrast to control mice, Tie-1-DeltaN mice developed a milder renal injury, reduced inflammation, and less albuminuria. RT-PCR showed significantly reduced expression of the NF-kappaB targets VCAM-1 and ICAM-1, compared with control mice. Thus, the data demonstrate a causal link between endothelial NF-kappaB activation and hypertension-induced renal damage. We conclude that in vivo NF-kappaB suppression in endothelial cells stops a signaling cascade leading to reduced hypertension-induced renal damage despite high blood pressure.
Keywords:Hypertension, Endothelium, NF-{kappa}B, Target-Organ Damage, Animals, Mice
Source:Circulation Research
ISSN:0009-7330
Publisher:American Heart Association (U.S.A.)
Volume:101
Number:3
Page Range:268-276
Date:3 August 2007
Official Publication:https://doi.org/10.1161/CIRCRESAHA.107.150474
PubMed:View item in PubMed

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