Sh. Wilson et al., Activated nuclear factor-kappa B is present in the coronary vasculature inexperimental hypercholesterolemia, ATHEROSCLER, 148(1), 2000, pp. 23-30
Citations number
29
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background: Experimental hypercholesterolemia (HC) is characterized by a de
crease in nitric oxide (NO) bioavailability and cellular proliferation. Nuc
lear factor-kappa B (NF-kappa B) is a transcriptional factor which plays a
coordinating role in inflammation and cellular proliferation and may be inv
olved in early atherosclerosis. We examined whether activated NF-kappa B wa
s present in experimental hypercholesterolemia in the coronary vasculature
in association with a decrease in NO bioavailability. Methods: A total of 1
4 juvenile domestic crossbred pigs were placed on a HC diet and six pigs on
a normal diet for 10-12 weeks. A monoclonal antibody to the activated form
of the p65 subunit of NF-kappa B was used to detect immunoreactivity in co
ronary artery sections. Coronary tissue homogenates were analyzed for activ
ated NF-kappa B and endothelial nitric oxide synthase (eNOS) using Western
blotting. In vitro coronary endothelium-dependent relaxation was performed
in response to bradykinin, as a measure of NO bioavailability. Results: Int
imal staining for activated NF-kappa B was present in 12/14 HC pigs as comp
ared with 0/6 controls (P < 0.001). Confocal microscopy confirmed the prese
nce of NF-kappa B in the nucleus of intimal cells although the majority of
the staining was cytoplasmic. In the HC group, Western blotting revealed an
increase in activated NF-kappa B in the vessel wall compared to the normal
group, in association with a decrease in the presence of eNOS protein and
an attenuated vasorelaxation response to bradykinin. Conclusion: This study
suggests a potential role for activation of NF-kappa B, in association wit
h a decrease in NO bioavailability, in the initial stages of atherosclerosi
s in the coronary vasculature. (C) 2000 Elsevier Science Ireland Ltd. All r
ights reserved.