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

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Item Type:	Article
Title:	Vascular endothelial cell-specific NF-kappaB suppression attenuates hypertension-induced renal damage
Creators Name:	Henke, N., Schmidt-Ullrich, R., Dechend, R., Park, J.K., Qadri, F., Wellner, M., Obst, M., Gross, V., Dietz, R., Luft, F.C., 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
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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