Published online before print June 21, 2007, doi: 10.1161/CIRCRESAHA.107.150474
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 12, 2007
Revised on June 3, 2007
Accepted on June 7, 2007
Vascular Endothelial Cell-Specific NF-
B Suppression Attenuates Hypertension-Induced Renal Damage
Norbert Henke ;
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.
* To whom correspondence should be addressed. 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 IB
N (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
Related Article:
-
Endothelial NF-B As a Mediator of Kidney Damage: The Missing Link Between Systemic Vascular and Renal Disease?
- Tomasz J. Guzik and David G. Harrison
Circ. Res. 2007 101: 227-229.[Full Text] [PDF]
This article has been cited by other articles:
 |
|
 |
|
  X. Ye, J. Ding, X. Zhou, G. Chen, and S. F. Liu Divergent roles of endothelial NF-{kappa}B in multiple organ injury and bacterial clearance in mouse models of sepsis J. Exp. Med., June 9, 2008; 205(6): 1303 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Shen, M. Hagiwara, Y.-Y. Yao, L. Chao, and J. Chao Salutary Effect of Kallistatin in Salt-Induced Renal Injury, Inflammation, and Fibrosis via Antioxidative Stress Hypertension, May 1, 2008; 51(5): 1358 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. E. Mann What's new in hypertension 2007? Nephrol. Dial. Transplant., February 1, 2008; 23(2): 466 - 470. [Full Text] [PDF]
|
|
|
|
|
|
A. Yogi, C. Mercure, J. Touyz, G. E. Callera, A. C.I. Montezano, A. B. Aranha, R. C. Tostes, T. Reudelhuber, and R. M. Touyz Renal Redox-Sensitive Signaling, but Not Blood Pressure, Is Attenuated by Nox1 Knockout in Angiotensin II-Dependent Chronic Hypertension Hypertension, February 1, 2008; 51(2): 500 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N Muller Mechanisms of hypertension-induced target organ damage Journal of Renin-Angiotensin-Aldosterone System, September 1, 2007; 8(3): 148 - 150. [PDF]
|
|
|
|
 |
|
 T. J. Guzik and D. G. Harrison Endothelial NF-{kappa}B As a Mediator of Kidney Damage: The Missing Link Between Systemic Vascular and Renal Disease? Circ. Res., August 3, 2007; 101(3): 227 - 229. [Full Text] [PDF]
|
|