Vascular endothelial cell-specific NF-kappaB suppression attenuates hypertension-induced renal damage.
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Vascular endothelial cell-specific NF-kappaB suppression attenuates hypertension-induced renal damage. / Henke, Norbert; Schmidt-Ullrich, Ruth; Dechend, Ralf; Park, Joon-Keun; Qadri, Fatimunnisa; Wellner, Maren; Obst, Michael; Gross, Volkmar; Dietz, Rainer; Luft, Friedrich C; Scheidereit, Claus; Muller, Dominik N.
In: CIRC RES, Vol. 101, No. 3, 3, 2007, p. 268-276.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Vascular endothelial cell-specific NF-kappaB suppression attenuates hypertension-induced renal damage.
AU - Henke, Norbert
AU - Schmidt-Ullrich, Ruth
AU - Dechend, Ralf
AU - Park, Joon-Keun
AU - Qadri, Fatimunnisa
AU - Wellner, Maren
AU - Obst, Michael
AU - Gross, Volkmar
AU - Dietz, Rainer
AU - Luft, Friedrich C
AU - Scheidereit, Claus
AU - Muller, Dominik N
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 101
SP - 268
EP - 276
JO - CIRC RES
JF - CIRC RES
SN - 0009-7330
IS - 3
M1 - 3
ER -
