Angiotensin II induces MMP-2 in a p47phox-dependent manner.
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.
Luchtefeld
Maren
M
Department of Cardiology and Angiology, Medizinische Hochschule Hannover, Germany.
Grote
Karsten
K
Grothusen
Christina
C
Bley
Sylvia
S
Bandlow
Nele
N
Selle
Tina
T
Strüber
Martin
M
Haverich
Axel
A
Bavendiek
Udo
U
Drexler
Helmut
H
Schieffer
Bernhard
B
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism*; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000172:deficiency / Q000378:metabolism*
D010750:Phosphoproteins; D000804:Angiotensin II; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D020778:Matrix Metalloproteinase 2