Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages

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• 作者：Hiroyuki Kinoshita^a ; ¹ ; Takeshi Matsumura^a ; ¹ ; ^{takeshim@gpo.kumamoto-u.ac.jp} ; Norio Ishii^a ; Kazuki Fukuda^a ; Takafumi Senokuchi^a ; Hiroyuki Motoshima^a ; Tatsuya Kondo^a ; Kayo Taketa^a ; Shuji Kawasaki^a ; Satoko Hanatani^a ; Motohiro Takeya^b ; Takeshi Nishikawa^a ; Eiichi Araki^a
• 关键词：Apocynin ; Reactive oxygen species ; NADPH oxidase ; Atherosclerosis ; Macrophages
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：8 February, 2013
• 年：2013
• 卷：431
• 期：2
• 页码：124-130
• 全文大小：837 K

文摘

Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progression of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE^-/-) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE^-/- mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE^-/- mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis.