The methyl xanthine caffeine inhibits DNA damage signaling and reactive species and reduces atherosclerosis in ApoE-/- mice

Mercer, J.R. , Gray, K., Figg, N., Kumar, S. and Bennett, M.R. (2012) The methyl xanthine caffeine inhibits DNA damage signaling and reactive species and reduces atherosclerosis in ApoE-/- mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(10), pp. 2461-2467. (doi: 10.1161/ATVBAHA.112.251322)

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Abstract

Objective—Caffeine remains one of the most widely consumed drugs in the world. Caffeine has multiple actions, including inhibition of the DNA damage response, and its metabolites, 1-methylxanthine and 1-methyluric acid, are potent antioxidants. Combined, these properties can exert direct effects on cell proliferation, cell death, inflammation, and DNA repair, all important processes that occur in atherosclerosis. Methods and Results—We first examined the effects of caffeine on mouse vascular smooth muscle cells. Caffeine inhibited activation of the DNA damage response regulator ataxia telangiectasia mutated protein and its downstream targets. Caffeine delayed DNA repair, had a concentration-dependent effect on cell proliferation, and protected against apoptosis. In vitro caffeine reduced oxygen consumption and decreased generation of reactive oxygen species. In vivo caffeine reduced DDR activation in vascular and nonvascular tissues, reduced reactive nitrogen species and serum levels of the DNA adduct 8-oxo-guanine, and inhibited atherogenesis in fat−fed ApoE−/− mice. Reduction in atherosclerosis was independent of the effects on blood pressure and serum lipids but associated with reduced cell proliferation and ataxia telangiectasia mutated protein activation. Conclusion—The Methyl Xanthine caffeine inhibits the DNA damage response in vitro and in vivo, regulates both cell proliferation and apoptosis after DNA damage, inhibits reactive species, and reduces atherogenesis in ApoE−/− mice.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mercer, Dr John
Authors: Mercer, J.R., Gray, K., Figg, N., Kumar, S., and Bennett, M.R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher:American Heart Association
ISSN:1079-5642
ISSN (Online):1524-4636

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