title: α1AMP-activated protein kinase mediates vascular protective effects of exercise.
abstract: OBJECTIVE
  We investigated whether AMP-activated protein kinase (AMPK) may be involved in the signaling processes leading to exercise-mediated vascular protection.
  
  
  RESULTS
  The effects of voluntary exercise on AMPK activity, endothelial NO synthase expression and phosphorylation, vascular reactive oxygen species formation, and cell senescence were tested in α1AMPK knockout and corresponding wild-type mice. Exercise significantly improved endothelial function, and increased plasma nitrite production in wild-type mice, associated with an activation of aortic AMPK assessed by its phosphorylation at threonine 172. In addition, regular physical activity resulted in an upregulation of endothelial NO synthase protein, serine 1177 endothelial NO synthase phosphorylation, and an increase of circulating Tie-2(+)Sca-1(+)Flk-1(+) myeloid progenitor cells. All these changes were absent after α1AMPK deletion. In addition, exercise increased the expression of important regulators of the antioxidative defense including heme oxygenase-1 and peroxisome proliferator-activated receptor γ coactivator 1α, decreased aortic reactive oxygen species levels, and prevented endothelial cell senescence in an α1AMPK-dependent manner.
  
  
  CONCLUSIONS
  Intact α1AMPK signaling is required for the signaling events leading to the manifestation of vascular protective effects during exercise. Pharmacological AMPK activation might be a novel approach in the near future to simulate the beneficial vascular effects of physical activity.
authors.affiliation: Department of Cardiology, Universitätsmedizin Mainz, Germany.
authors.forename: Swenja
authors.initials: S
authors.lastname: Kröller-Schön
authors.forename: Thomas
authors.initials: T
authors.lastname: Jansen
authors.forename: Felix
authors.initials: F
authors.lastname: Hauptmann
authors.forename: Andrea
authors.initials: A
authors.lastname: Schüler
authors.forename: Tjebo
authors.initials: T
authors.lastname: Heeren
authors.forename: Michael
authors.initials: M
authors.lastname: Hausding
authors.forename: Matthias
authors.initials: M
authors.lastname: Oelze
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.forename: John F
authors.initials: JF
authors.lastname: Keaney
authors.forename: Philip
authors.initials: P
authors.lastname: Wenzel
authors.forename: Andreas
authors.initials: A
authors.lastname: Daiber
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schulz
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000097:blood / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016922:Cellular Senescence; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D012038:Regeneration; D015398:Signal Transduction
chemical_list: D009573:Nitrites; D000255:Adenosine Triphosphate; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases