Caffeine enhances endothelial repair by an AMPK-dependent mechanism.
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.
Spyridopoulos
Ioakim
I
Department of Internal Medicine III, University of Frankfurt, Germany. spyridopoulos@uni-frankfurt.de
Fichtlscherer
Stephan
S
Popp
Rüdiger
R
Toennes
Stefan W
SW
Fisslthaler
Beate
B
Trepels
Thomas
T
Zernecke
Alma
A
Liehn
Elisa A
EA
Weber
Christian
C
Zeiher
Andreas M
AM
Dimmeler
Stefanie
S
Haendeler
Judith
J