title: Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages.
abstract: 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.
authors: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors: Hiroyuki
authors: H
authors: Kinoshita
authors: Takeshi
authors: T
authors: Matsumura
authors: Norio
authors: N
authors: Ishii
authors: Kazuki
authors: K
authors: Fukuda
authors: Takafumi
authors: T
authors: Senokuchi
authors: Hiroyuki
authors: H
authors: Motoshima
authors: Tatsuya
authors: T
authors: Kondo
authors: Kayo
authors: K
authors: Taketa
authors: Shuji
authors: S
authors: Kawasaki
authors: Satoko
authors: S
authors: Hanatani
authors: Motohiro
authors: M
authors: Takeya
authors: Takeshi
authors: T
authors: Nishikawa
authors: Eiichi
authors: E
authors: Araki
mesh_terms: D000098:Acetophenones / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors
chemical_list: D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D016179:Granulocyte Colony-Stimulating Factor; C056165:acetovanillone