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.
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Authors | Maren Luchtefeld, Karsten Grote, Christina Grothusen, Sylvia Bley, Nele Bandlow, Tina Selle, Martin Strüber, Axel Haverich, Udo Bavendiek, Helmut Drexler, Bernhard Schieffer |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 328
Issue 1
Pg. 183-8
(Mar 04 2005)
ISSN: 0006-291X [Print] United States |
PMID | 15670768
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Phosphoproteins
- Angiotensin II
- NADPH Oxidases
- neutrophil cytosolic factor 1
- Matrix Metalloproteinase 2
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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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