on August 28, 2008
Published online before print August 28, 2008, doi: 10.1161/ATVBAHA.108.174060
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Submitted on February 24, 2008
Accepted on August 14, 2008
Caffeine Enhances Endothelial Repair by an AMPK-Dependent Mechanism
Ioakim Spyridopoulos ;
From Molecular Cardiology, Department of Internal Medicine III (I.M., S.F., T.T., A.M.Z., S.D., J.H.), University of Frankfurt, Germany; the Department of Physiology (R.P., B.F.), University of Frankfurt, Germany; the Department of Forensic Toxicology (S.W.T.), University of Frankfurt, Germany; the Institute for Molecular Cardiovascular Research (IMCAR) (A.Z., E.A.L., C.W.), RWTH Aachen University, Germany.
* To whom correspondence should be addressed. E-mail: juhae001{at}uni-duesseldorf.de.
Objective—Migratory capacity of endothelial progenitor cells (EPCs) and mature endothelial cells (ECs) is a key prerequisite for endothelial repair after denuding injury or endothelial damage.
Methods and Results—We demonstrate that caffeine in physiologically relevant concentrations (50 to 100 µmol/L) induces migration of human EPCs as well as mature ECs. In patients with coronary artery disease (CAD), caffeinated coffee increased caffeine serum concentration from 2 µmol/L to 23 µmol/L, coinciding with a significant increase in migratory activity of patient-derived EPCs. Decaffeinated coffee neither affected caffeine serum levels nor migratory capacity of EPCs. Treatment with caffeine for 7 to 10 days in a mouse-model improved endothelial repair after denudation of the carotid artery. The enhancement of reendothelialization by caffeine was significantly reduced in AMPK knockout mice compared to wild-type animals. Transplantation of wild-type and AMPK-/- bone marrow into wild-type mice revealed no difference in caffeine challenged reendothelialization. ECs which were depleted of mitochondrial DNA did not migrate when challenged with caffeine, suggesting a potential role for mitochondria in caffeine-dependent migration.
Conclusion—These results provide evidence that caffeine enhances endothelial cell migration and reendothelialization in part through an AMPK-dependent mechanism, suggesting a beneficial role for caffeine in endothelial repair.
Key words: caffeine • reendothelialization • endothelium • AMPK • mitochondria
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