Caffeine Enhances Endothelial Repair by an AMPK-Dependent Mechanism

Arteriosclerosis, Thrombosis, and Vascular Biology - Tập 28 Số 11 - Trang 1967-1974 - 2008
Ioakim Spyridopoulos1,2,3,4, Stephan Fichtlscherer1,5,3,4, Rüdiger Popp1,3,4, Stefan W. Toennes1,3,4,6, Beate Fißlthaler7,1,3,4, Thomas Trepels1,8,3,4, Alma Zernecke9,1,3,4, Elisa A. Liehn10,1,3,4, Christian Weber11,1,3,4, Andreas M. Zeiher12,1,3,4, Stefanie Dimmeler1,13,3,4, Judith Haendeler1,14,3,4
1From Molecular Cardiology, Department of Internal Medicine III (I.M., I.S., 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. Current affiliation for J.H.: Molecular Cell & Aging Research, Institut fuer...
2Ioakim Spyridopoulos From Molecular Cardiology, Department of Internal Medicine III (I.M., I.S., S.F., T.T., A.M.Z., S.D., J.H.), University of Frankfurt, Germany
3the Department of Forensic Toxicology (S.W.T.), University of Frankfurt, Germany
4the Department of Physiology (R.P., B.F.), University of Frankfurt, Germany
5Stephan Fichtlscherer From Molecular Cardiology, Department of Internal Medicine III (I.M., I.S., S.F., T.T., A.M.Z., S.D., J.H.), University of Frankfurt, Germany
6the Institute for Molecular Cardiovascular Research (IMCAR) (A.Z., E.A.L., C.W.), RWTH Aachen University, Germany. Current affiliation for J.H.: Molecular Cell & Aging Research, Institut fuer umweltmedizinische Forschung (IUF), University of Duesseldorf GmbH, Germany.
7Beate Fisslthaler From Molecular Cardiology, Department of Internal Medicine III (I.M., I.S., S.F., T.T., A.M.Z., S.D., J.H.), University of Frankfurt, Germany
8Thomas Trepels From Molecular Cardiology, Department of Internal Medicine III (I.M., I.S., S.F., T.T., A.M.Z., S.D., J.H.), University of Frankfurt, Germany
9Alma Zernecke From Molecular Cardiology, Department of Internal Medicine III (I.M., I.S., S.F., T.T., A.M.Z., S.D., J.H.), University of Frankfurt, Germany
10Elisa A. Liehn From Molecular Cardiology, Department of Internal Medicine III (I.M., I.S., S.F., T.T., A.M.Z., S.D., J.H.), University of Frankfurt, Germany
11Christian Weber From Molecular Cardiology, Department of Internal Medicine III (I.M., I.S., S.F., T.T., A.M.Z., S.D., J.H.), University of Frankfurt, Germany
12Andreas M. Zeiher From Molecular Cardiology, Department of Internal Medicine III (I.M., I.S., S.F., T.T., A.M.Z., S.D., J.H.), University of Frankfurt, Germany
13Stefanie Dimmeler From Molecular Cardiology, Department of Internal Medicine III (I.M., I.S., S.F., T.T., A.M.Z., S.D., J.H.), University of Frankfurt, Germany
14Judith Haendeler From Molecular Cardiology, Department of Internal Medicine III (I.M., I.S., S.F., T.T., A.M.Z., S.D., J.H.), University of Frankfurt, Germany

Tóm tắt

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.

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Thông tin xuất bản

Arteriosclerosis, Thrombosis, and Vascular Biology

Tập 28 Số 11

1967-1974

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