Role for Nox1 NADPH oxidase in atherosclerosis

Andrea L Sheehan1, Samuel Carrell, Bryon Johnson

  • 1Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, United States.

Atherosclerosis
|March 18, 2011
PubMed
Abstract

Insights

Nox1 NADPH oxidase contributes to atherosclerosis by increasing superoxide levels and lesion size. Its deficiency in mice reduced atherosclerotic lesions and macrophage infiltration, indicating its role in disease progression.

Area of Science:

  • Cardiovascular Research
  • Oxidative Stress Biology
  • Molecular Medicine

Background:

  • Atherosclerosis is a chronic inflammatory disease of arteries.
  • NADPH oxidases (Nox) are implicated in oxidative stress and cardiovascular pathology.
  • Nox1's specific role in atherogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the contribution of Nox1 NADPH oxidase to the development of atherosclerosis.
  • To determine the impact of Nox1 deficiency on atherosclerotic lesion characteristics in a mouse model.

Main Methods:

  • Apolipoprotein E-deficient mice (ApoE(-/-)) and dual-deficient ApoE(-/-) Nox1(-/y) mice were fed an atherogenic diet for 18 weeks.
  • Superoxide levels, lesion area, macrophage infiltration, and intimal hyperplasia were assessed.
  • Carotid artery ligation was performed to induce intimal hyperplasia.

Main Results:

  • Nox1 deficiency significantly reduced aortic arch lesion area (43% to 28%) and superoxide levels.
  • Reduced lesion size in Nox1-deficient mice was associated with decreased macrophage infiltration.
  • Inhibition of Nox1 attenuated intimal hyperplasia, decreasing cellular proliferation and increasing collagen content.

Conclusions:

  • Nox1-derived reactive oxygen species (ROS) are critical in modifying atherosclerotic lesion composition.
  • Nox1 plays a significant role in promoting lesion size and progression in a murine model of atherosclerosis.

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