title: Caffeine enhances endothelial repair by an AMPK-dependent mechanism.
abstract: 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.
  
  
  RESULTS
  We demonstrate that caffeine in physiologically relevant concentrations (50 to 100 micromol/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 micromol/L to 23 micromol/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine III, University of Frankfurt, Germany. spyridopoulos@uni-frankfurt.de
authors.forename: Ioakim
authors.initials: I
authors.lastname: Spyridopoulos
authors.forename: Stephan
authors.initials: S
authors.lastname: Fichtlscherer
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Popp
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Toennes
authors.forename: Beate
authors.initials: B
authors.lastname: Fisslthaler
authors.forename: Thomas
authors.initials: T
authors.lastname: Trepels
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Liehn
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Judith
authors.initials: J
authors.lastname: Haendeler