Pleiotropic effects of acarbose on atherosclerosis development in rabbits are mediated via upregulating AMPK signals

• Published in: Scientific reports 2016-12, Vol.6 (1), p.38642-38642, Article 38642
• Main Authors: Chan, Kuei-Chuan, Yu, Meng-Hsun, Lin, Ming-Cheng, Huang, Chien-Ning, Chung, Dai-Jung, Lee, Yi-Ju, Wu, Cheng-Hsun, Wang, Chau-Jong
• Format: Article
• Language: English
• Subjects: 13; 13/51; 631/45; 631/80; 82/29; Acarbose; Actin; Aorta; Arteriosclerosis; Atherosclerosis; Cholesterol; Glucose tolerance; High cholesterol diet; Humanities and Social Sciences; Immunohistochemistry; Interleukin 6; Intolerance; Low density lipoprotein; multidisciplinary; Myocardial infarction; Nitric oxide; Nitric-oxide synthase; Proliferating cell nuclear antigen; Rabbits; Ras protein; Science; Senescence; Serum levels; Tumor necrosis factor; α-Glucosidase; β-Galactosidase
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep38642

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.