Caffeine enhances endothelial repair by an AMPK-dependent mechanism

Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1967-74. doi: 10.1161/ATVBAHA.108.174060. Epub 2008 Aug 28.

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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Adenosine Triphosphate / metabolism
  • Adult
  • Animals
  • Bone Marrow Transplantation
  • Caffeine / blood
  • Caffeine / pharmacology*
  • Carotid Artery Injuries / drug therapy
  • Carotid Artery Injuries / enzymology
  • Carotid Artery Injuries / pathology
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Coffee
  • Coronary Artery Disease / enzymology
  • Coronary Artery Disease / pathology
  • DNA, Mitochondrial / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects*
  • Endothelial Cells / enzymology
  • Endothelial Cells / pathology
  • Energy Metabolism / drug effects
  • Female
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Multienzyme Complexes / deficiency
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Stem Cells / drug effects*
  • Stem Cells / enzymology
  • Stem Cells / pathology
  • Time Factors

Substances

  • Coffee
  • DNA, Mitochondrial
  • Multienzyme Complexes
  • Caffeine
  • Adenosine Triphosphate
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases