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

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• 作者：Luchtefeld ; Maren ; Grote ; Karsten ; Grothusen ; Christina ; Bley ; Sylvia ; Bandlow ; Nele ; Selle ; Tina ; et. al.
• 关键词：Angiotensin II ; MMP-2 ; NAD(P)H-oxidase ; Atherosclerosis
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2005
• 出版时间：March 4, 2005
• 年：2005
• 卷：328
• 期：1
• 页码：183-188
• 全文大小：539 K

文摘

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 NAD(P)H-oxidase-dependent ROS formation, we assessed whether ANG II induces MMP-2 in a NAD(P)H-oxidase-dependent manner. MMP-2 mRNA expression and activity were analyzed in wildtype and p47phox-deficient (p47phox^aaa/aaa) 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 aa-smooth muscle cell actin (aa-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 aa-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.