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

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.

journal_name

Circ Res

journal_title

Circulation research

authors

Henke N,Schmidt-Ullrich R,Dechend R,Park JK,Qadri F,Wellner M,Obst M,Gross V,Dietz R,Luft FC,Scheidereit C,Muller DN

doi

10.1161/CIRCRESAHA.107.150474

subject

Has Abstract

pub_date

2007-08-03 00:00:00

pages

268-76

issue

3

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.107.150474

journal_volume

101

pub_type

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