Activated nuclear factor-κB is present in the coronary vasculature in experimental hypercholesterolemia

Stephanie H. Wilson, Noel M. Caplice, Robert D. Simari, David Holmes, Paula J. Carlson, Amir Lerman

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Background: Experimental hypercholesterolemia (HC) is characterized by a decrease in nitric oxide (NO) bioavailability and cellular proliferation. Nuclear factor-κB (NF-κB) is a transcriptional factor which plays a coordinating role in inflammation and cellular proliferation and may be involved in early atherosclerosis. We examined whether activated NF-κB was present in experimental hypercholesterolemia in the coronary vasculature in association with a decrease in NO bioavailability. Methods: A total of 14 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-κB was used to detect immunoreactivity in coronary artery sections. Coronary tissue homogenates were analyzed for activated NF-κB 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: Intimal staining for activated NF-κB was present in 12/14 HC pigs as compared with 0/6 controls (P<0.001). Confocal microscopy confirmed the presence of NF-κB 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-κB 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-κB, in association with a decrease in NO bioavailability, in the initial stages of atherosclerosis in the coronary vasculature. Copyright (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)23-30
Number of pages8
JournalAtherosclerosis
Volume148
Issue number1
DOIs
StatePublished - Jan 2000

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Hypercholesterolemia
Biological Availability
Nitric Oxide
Tunica Intima
Nitric Oxide Synthase Type III
Bradykinin
Swine
Western Blotting
Cell Proliferation
Staining and Labeling
Diet
Sus scrofa
Cell Nucleus
Confocal Microscopy
Vasodilation
Endothelium
Coronary Artery Disease
Atherosclerosis
Coronary Vessels
Monoclonal Antibodies

Keywords

  • Endothelial dysfunction
  • Hypercholesterolemia
  • Nuclear factor-κB

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Activated nuclear factor-κB is present in the coronary vasculature in experimental hypercholesterolemia. / Wilson, Stephanie H.; Caplice, Noel M.; Simari, Robert D.; Holmes, David; Carlson, Paula J.; Lerman, Amir.

In: Atherosclerosis, Vol. 148, No. 1, 01.2000, p. 23-30.

Research output: Contribution to journalArticle

Wilson, Stephanie H. ; Caplice, Noel M. ; Simari, Robert D. ; Holmes, David ; Carlson, Paula J. ; Lerman, Amir. / Activated nuclear factor-κB is present in the coronary vasculature in experimental hypercholesterolemia. In: Atherosclerosis. 2000 ; Vol. 148, No. 1. pp. 23-30.
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AB - Background: Experimental hypercholesterolemia (HC) is characterized by a decrease in nitric oxide (NO) bioavailability and cellular proliferation. Nuclear factor-κB (NF-κB) is a transcriptional factor which plays a coordinating role in inflammation and cellular proliferation and may be involved in early atherosclerosis. We examined whether activated NF-κB was present in experimental hypercholesterolemia in the coronary vasculature in association with a decrease in NO bioavailability. Methods: A total of 14 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-κB was used to detect immunoreactivity in coronary artery sections. Coronary tissue homogenates were analyzed for activated NF-κB 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: Intimal staining for activated NF-κB was present in 12/14 HC pigs as compared with 0/6 controls (P<0.001). Confocal microscopy confirmed the presence of NF-κB 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-κB 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-κB, in association with a decrease in NO bioavailability, in the initial stages of atherosclerosis in the coronary vasculature. Copyright (C) 2000 Elsevier Science Ireland Ltd.

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