Acetylcholinesterase inhibitors attenuate atherogenesis in apolipoprotein E-knockout mice

Keita Inanaga, Toshihiro Ichiki, Ryohei Miyazaki, Kotaro Takeda, Toru Hashimoto, Hirohide Matsuura, Kenji Sunagawa

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objective: Donepezil, a reversible acetylcholinesterase inhibitor, improves cognitive function of Alzheimer's disease. Stimulation of cholinergic system was reported to improve long-term survival of rats with chronic heart failure and to attenuate inflammatory response in mice with lipopolysaccharide-induced sepsis. We sought to determine whether the pharmacological stimulation of cholinergic system by donepezil reduces atherogenesis in apolipoprotein (Apo) E-knockout (KO) mice. Methods and results: Male ApoE-KO mice (10-week-old) were fed a high-fat diet and received infusion of angiotensin (Ang) II (490 ng/kg/day). Donepezil or physostigmine was administered for 4 weeks. Oral administration of donepezil (5 mg/kg/day) or infusion of physostigmine (2 mg/kg/day) significantly attenuated atherogenesis (Oil Red O-positive area) without significant changes in heart rate, blood pressure and total cholesterol levels. Administration of donepezil suppressed expression of monocyte chemoattractant protein-1 and tumor necrosis factor-α, NADPH oxidase activity and production of reactive oxygen species in the aorta. Conclusion: The present study revealed novel anti-oxidative and anti-atherosclerotic effects of pharmacological stimulation of cholinergic system by donepezil. Donepezil may be used as a novel therapeutics for the atherosclerotic cardiovascular diseases.

Original languageEnglish
Pages (from-to)52-58
Number of pages7
JournalAtherosclerosis
Volume213
Issue number1
DOIs
Publication statusPublished - Nov 1 2010

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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