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Angiotensin II induces MMP-2 in a p47phox-dependent manner.

Abstract
Activated matrix metalloproteinases (MMPs) in patients with acute coronary syndromes may contribute to plaque destabilization. Since reactive oxygen species (ROS) induce MMP-2 and angiotensin II (ANG II) enhances NADPH-oxidase-dependent ROS formation, we assessed whether ANG II induces MMP-2 in a NADPH-oxidase-dependent manner. MMP-2 mRNA expression and activity were analyzed in wildtype and p47phox-deficient (p47phox-/-) murine smooth muscle cells (SMC). To address a clinical implication, sections of human atherosclerotic arteries were stained for MMP-2, p47phox, ANG II, AT1-receptor, and alpha-smooth muscle cell actin (alpha-SMC actin). MMP-2 protein expression and activity from these arteries were compared to those without atherosclerosis. ANG II enhances mRNA synthesis and activity of MMP-2 in a p47phox-dependent manner. Immunohistochemical analyses revealed a co-localization of MMP-2 with p47phox, ANG II, AT1-receptor, and alpha-SMC actin. MMP-2 protein expression and gelatinolytic activity are increased in atherosclerotic arteries. Thus, activation of the renin-angiotensin system may contribute to plaque destabilization via ROS-dependent induction of MMP-2.
AuthorsMaren Luchtefeld, Karsten Grote, Christina Grothusen, Sylvia Bley, Nele Bandlow, Tina Selle, Martin Strüber, Axel Haverich, Udo Bavendiek, Helmut Drexler, Bernhard Schieffer
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 328 Issue 1 Pg. 183-8 (Mar 04 2005) ISSN: 0006-291X [Print] United States
PMID15670768 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Phosphoproteins
  • Angiotensin II
  • NADPH Oxidases
  • neutrophil cytosolic factor 1
  • Matrix Metalloproteinase 2
Topics
  • Angiotensin II (pharmacology)
  • Animals
  • Cardiomyopathies (metabolism)
  • Cells, Cultured
  • Coronary Artery Disease (metabolism)
  • Coronary Vessels (metabolism)
  • Dose-Response Relationship, Radiation
  • Humans
  • In Vitro Techniques
  • Matrix Metalloproteinase 2 (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Myocytes, Smooth Muscle (drug effects, metabolism)
  • NADPH Oxidases
  • Phosphoproteins (deficiency, metabolism)

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