title: Pleiotropic effects of acarbose on atherosclerosis development in rabbits are mediated via upregulating AMPK signals.
abstract: Acarbose, an α-glucosidase inhibitor, is reported to reduce the incidence of silent myocardial infarction and slow the progression of intima-media thickening in patients with glucose intolerance. Here we investigate other impacts of acarbose on atherosclerosis development and the underlying mechanisms of atherosclerosis initiation and progression in vivo and in vitro. Rabbits fed a high cholesterol diet (HCD) were treated with acarbose (2.5-5.0 mg kg-1). Immunohistochemistry was used to assess the expression of inducible nitric oxide synthase (iNOS), Ras, proliferating cell nuclear antigen (PCNA), IL-6, β-galactosidase, and p-AMPK in atherosclerotic lesions. Treatment with acarbose in HCD-fed rabbits was found to significantly reduce the severity of aortic atheroma and neointimal expression of α-actin, PCNA, IL-6, TNF-α, Ras, and β-galactosidase; to significantly increase expression of iNOS and p-AMPK, but not to affect serum levels of glucose, total cholesterol, and LDL. Western blot analysis showed acarbose dose-dependently decreased β-galactosidase and Ras expression and increased p-AMPK expression in TNF-α-treated A7r5 cells. In addition, acarbose restored p-AMPK and iNOS levels in AMPK inhibitor- and iNOS inhibitor-treated A7r5 cells, respectively. In conclusion, acarbose can pleiotropically inhibit rabbit atherosclerosis by reducing inflammation, senescence, and VSMCs proliferation/migration via upregulating AMPK signals.
authors.affiliation: Department of Internal Medicine, Chung-Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan.|School of Medicine, Institute of Medicine, Chung-Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan.
authors.forename: Kuei-Chuan
authors.initials: KC
authors.lastname: Chan
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung 402, Taiwan.
authors.forename: Meng-Hsun
authors.initials: MH
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, Chung-Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan.|School of Medicine, Institute of Medicine, Chung-Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, Chung-Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan.|School of Medicine, Institute of Medicine, Chung-Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan.
authors.forename: Chien-Ning
authors.initials: CN
authors.lastname: Huang
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung 402, Taiwan.
authors.forename: Dai-Jung
authors.initials: DJ
authors.lastname: Chung
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung 402, Taiwan.|Department of Pathology, Chung Shan Medical University Hospital, School of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy, China Medical University, Taichung, 404, Taiwan.
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung 402, Taiwan.|Department of Medical Research, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan.
authors.forename: Chau-Jong
authors.initials: CJ
authors.lastname: Wang
mesh_terms: D020909:Acarbose / Q000009:adverse effects*; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D065089:Glycoside Hydrolase Inhibitors / Q000009:adverse effects*; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits
chemical_list: D015415:Biomarkers; D065089:Glycoside Hydrolase Inhibitors; D008055:Lipids; D020909:Acarbose