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Phagocytic NADPH oxidase-dependent superoxide production stimulates matrix metalloproteinase-9: implications for

Guillermo Zalba1, Ana Fortuño, Josune Orbe

  • 1Division of Cardiovascular Sciences, Centre for Applied Medical Research, University Clinic, School of Medicine, University of Navarra, Pamplona, Spain. gzalba@unav.es

Arteriosclerosis, Thrombosis, and Vascular Biology
|December 30, 2006
PubMed
Abstract

Insights

Phagocytic NADPH oxidase activation boosts matrix metalloproteinase-9 (MMP-9) in monocytes, a key factor in atherosclerosis. This link suggests MMP-9 mediates oxidative stress in the atherosclerotic process.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Biochemistry

Background:

  • Matrix metalloproteinase-9 (MMP-9) plays a role in atherosclerosis.
  • Phagocytic NADPH oxidase is also implicated in the development of atherosclerosis.

Purpose of the Study:

  • To investigate the association between phagocytic NADPH oxidase and MMP-9 in human atherosclerosis.

Main Methods:

  • In vitro studies on human monocytes using ELISA and zymography.
  • Immunohistochemical analysis of carotid endarterectomies.
  • Measurement of superoxide production and plasma MMP-9 levels in asymptomatic subjects.

Main Results:

  • NADPH oxidase activation increased MMP-9 secretion and activity in monocytes.
  • Phagocytic NADPH oxidase colocalized with MMP-9 in atherosclerotic lesions.
  • A significant positive correlation was observed between NADPH oxidase activity and plasma MMP-9 levels in asymptomatic individuals.
  • Higher superoxide production correlated with increased MMP-9, oxidized LDL, nitrotyrosine, and carotid atherosclerosis markers.

Conclusions:

  • Enhanced NADPH oxidase activity stimulates MMP-9 production in monocytes, potentially contributing to atherosclerosis.
  • MMP-9 acts as a crucial mediator of phagocytic NADPH oxidase-driven oxidative stress in the atherosclerotic process.

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