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

S H Wilson1, N M Caplice, R D Simari

  • 1Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.

Atherosclerosis
|December 2, 1999
PubMed

Insights

Activated nuclear factor-kappaB (NF-kappaB) was found in pigs with experimental hypercholesterolemia, linked to reduced nitric oxide (NO) bioavailability and early atherosclerosis. This suggests NF-kappaB activation plays a role in the initial stages of this vascular disease.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Pathology

Background:

  • Experimental hypercholesterolemia (HC) is associated with reduced nitric oxide (NO) bioavailability and cellular proliferation.
  • Nuclear factor-kappaB (NF-kappaB) is implicated in inflammation, cellular proliferation, and potentially early atherosclerosis.

Purpose of the Study:

  • To investigate the presence of activated NF-kappaB in the coronary vasculature of experimental hypercholesterolemia.
  • To determine if activated NF-kappaB is associated with decreased NO bioavailability in this condition.

Main Methods:

  • Pigs were fed either a hypercholesterolemic (HC) or normal diet for 10-12 weeks.
  • Activated NF-kappaB was detected using monoclonal antibodies and Western blotting in coronary artery tissues.
  • Endothelium-dependent vasorelaxation and nitric oxide (NO) bioavailability were assessed in vitro.

Main Results:

  • Activated NF-kappaB was significantly present in the coronary vasculature of HC pigs compared to controls.
  • The HC group showed increased activated NF-kappaB, decreased endothelial nitric oxide synthase (eNOS) protein, and impaired vasorelaxation.
  • NF-kappaB was detected in both the nucleus and cytoplasm of intimal cells.

Conclusions:

  • Activation of NF-kappaB is suggested to play a role in the early stages of atherosclerosis.
  • The findings link NF-kappaB activation with reduced NO bioavailability in the coronary vasculature during hypercholesterolemia.
Abstract

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