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

Area of Science:

• Cardiovascular Research
• Pharmacology
• Molecular Biology

Background:

• Acarbose, an α-glucosidase inhibitor, previously showed benefits in cardiovascular health.
• Its broader effects on atherosclerosis and underlying mechanisms require further investigation.

Purpose of the Study:

• To investigate the impact of acarbose on atherosclerosis development and progression.
• To elucidate the molecular mechanisms by which acarbose affects atherosclerosis in vivo and in vitro.

Main Methods:

• Rabbits on a high-cholesterol diet were treated with acarbose.
• Immunohistochemistry and Western blot analysis were used to assess molecular markers in aortic lesions and cell cultures.
• In vitro studies utilized TNF-α-treated A7r5 cells with and without inhibitor treatments.

Main Results:

• Acarbose significantly reduced aortic atheroma severity and neointimal expression of inflammatory and senescence markers (PCNA, IL-6, TNF-α, Ras, β-galactosidase).
• Acarbose increased the expression of inducible nitric oxide synthase (iNOS) and phosphorylated AMP-activated protein kinase (p-AMPK).
• In vitro, acarbose dose-dependently decreased β-galactosidase and Ras, while increasing p-AMPK, and restored p-AMPK and iNOS levels.

Conclusions:

• Acarbose exhibits pleiotropic effects in inhibiting rabbit atherosclerosis.
• It reduces inflammation, senescence, and vascular smooth muscle cell proliferation/migration.
• These effects are mediated through the upregulation of AMPK signaling pathways.