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(Circulation Research. 2007;101:268.)
© 2007 American Heart Association, Inc.

Molecular Medicine

Vascular Endothelial Cell–Specific NF-B Suppression Attenuates Hypertension-Induced Renal Damage

Norbert Henke, Ruth Schmidt-Ullrich, Ralf Dechend, Joon-Keun Park, Fatimunnisa Qadri, Maren Wellner, Michael Obst, Volkmar Gross, Rainer Dietz, Friedrich C. Luft, Claus Scheidereit, Dominik N. Muller

From the Medical Faculty of the Charité (N.H., R.D., M.W., R.D., F.C.L., D.N.M.), Franz Volhard Clinic, HELIOS Klinikum-Berlin; the Max-Delbrück-Center for Molecular Medicine (R.S.-U., F.Q., M.O., V.G., F.C.L., C.S., D.N.M.), Berlin-Buch; and the Medical School of Hannover (J.-K.P.), Hannover, Germany.

Correspondence to Ruth Schmidt-Ullrich, PhD, Max-Delbrück-Center, Robert-Rossle Street 50, 13125 Berlin-Buch, Germany. E-mail rschmidt{at}mdc-berlin.de

Nuclear factor kappa B (NF-B) participates in hypertension-induced vascular and target-organ damage. We tested whether or not endothelial cell–specific NF-B suppression would be ameliorative. We generated Cre/lox transgenic mice with endothelial cell–restricted NF-B super-repressor IBN (Tie-1-N mice) overexpression. We confirmed cell-specific IBN expression and reduced NF-B activity after TNF- 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-N and control mice. In contrast to control mice, Tie-1-N mice developed a milder renal injury, reduced inflammation, and less albuminuria. RT-PCR showed significantly reduced expression of the NF-B targets VCAM-1 and ICAM-1, compared with control mice. Thus, the data demonstrate a causal link between endothelial NF-B activation and hypertension-induced renal damage. We conclude that in vivo NF-B suppression in endothelial cells stops a signaling cascade leading to reduced hypertension-induced renal damage despite high blood pressure.

Key Words: hypertension • endothelium • NF-B • target-organ damage

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