Published online before print July 17, 2003, doi: 10.1161/01.RES.0000086942.13523.88
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Submitted on February 24, 2003
Revised on June 23, 2003
Accepted on July 8, 2003
Pressure-Induced Vascular Activation of Nuclear Factor-
B. Role in Cell Survival
Catherine A. Lemarié ;
From Inserm U541, Hôpital Lariboisière, Paris, France.
* To whom correspondence should be addressed. E-mail: lehoux{at}larib.inserm.fr.
The effects of mechanical factors on nuclear factor (NF)-
B activation and its potential functional roles have been very little explored in the intact vessel. Thus, we chose to study the regulation of NF-B by intraluminal pressure using an organ culture model of mouse carotid arteries maintained at 80 or 150 mm Hg during 24 hours. Gel shift analysis revealed an increase in the DNA-binding capacity of NF-B in vessels at high pressure compared with vessels at normal pressure (304±49%; P<0.001). This coincided with reduced levels of the endogenous NF-B inhibitor IB
in arteries at 150 mm Hg (52±7%; P<0.001), as detected by Western blot. To study the functional role of the pressure-induced activation of NF-B, we evaluated the rate of apoptosis (TUNEL method) in carotid arteries cultured with or without an inhibitor peptide blocking nuclear translocation of NF-B. No apoptosis was detected in control arteries either at 80 or 150 mm Hg. However, in the presence of the NF-B inhibitor peptide, we observed apoptosis in vessels at 80 mm Hg (5±1%; P<0.001 versus untreated controls), which was markedly increased in vessels at 150 mm Hg (14±2%; P<0.001). These results were corroborated by immunohistochemical analysis showing positive staining for cleaved caspase 3 in vessels at 80 mm Hg treated with the NF-B inhibitor peptide, which was additionally enhanced in treated vessels at 150 mm Hg. Our findings demonstrate that high intraluminal pressure activates NF-B in arteries. Moreover, the activation of NF-B seems to play a key role in preventing apoptosis in vascular cells, especially when vessels are exposed to high intraluminal pressure.
Key words: mechanical stress • stretch • hypertension • vascular remodeling • apoptosis
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