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Article Dans Une Revue Antioxidants Année : 2021

Lack of Endothelial α1AMPK Reverses the Vascular Protective Effects of Exercise by Causing eNOS Uncoupling

Thomas Jansen
Miroslava Kvandová
Isabella Schmal
Sanela Kalinovic
Paul Stamm
  • Fonction : Auteur
Marin Kuntic
Marc Foretz
Benoit Viollet
Andreas Daiber
Matthias Oelze
  • Fonction : Auteur
John Keaney
  • Fonction : Auteur
Thomas Münzel
Eberhard Schulz
  • Fonction : Auteur
Swenja Kröller-Schön
  • Fonction : Auteur

Résumé

Voluntary exercise training is an effective way to prevent cardiovascular disease, since it results in increased NO bioavailability and decreased reactive oxygen species (ROS) production. AMP-activated protein kinase (AMPK), especially its α1AMPK subunit, modulates ROS-dependent vascular homeostasis. Since endothelial cells play an important role in exercise-induced changes of vascular signaling, we examined the consequences of endothelial-specific α1AMPK deletion during voluntary exercise training. We generated a mouse strain with specific deletion of α1AMPK in endothelial cells (α1AMPKflox/flox x TekCre+). While voluntary exercise training improved endothelial function in wild-type mice, it had deleterious effects in mice lacking endothelial α1AMPK indicated by elevated reactive oxygen species production (measured by dihydroethidum fluorescence and 3-nitrotyrosine staining), eNOS uncoupling and endothelial dysfunction. Importantly, the expression of the phagocytic NADPH oxidase isoform (NOX-2) was down-regulated by exercise in control mice, whereas it was up-regulated in exercising α1AMPKflox/flox x TekCre+ animals. In addition, nitric oxide bioavailability was decreased and the antioxidant/protective nuclear factor erythroid 2-related factor 2 (Nrf-2) response via heme oxygenase 1 and uncoupling protein-2 (UCP-2) was impaired in exercising α1AMPKflox/flox x TekCre+ mice. Our results demonstrate that endothelial α1AMPK is a critical component of the signaling events that enable vascular protection in response to exercise. Moreover, they identify endothelial α1AMPK as a master switch that determines whether the effects of exercise on the vasculature are protective or detrimental.
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hal-03845780 , version 1 (09-11-2022)

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Thomas Jansen, Miroslava Kvandová, Isabella Schmal, Sanela Kalinovic, Paul Stamm, et al.. Lack of Endothelial α1AMPK Reverses the Vascular Protective Effects of Exercise by Causing eNOS Uncoupling. Antioxidants , 2021, 10 (12), pp.1974. ⟨10.3390/antiox10121974⟩. ⟨hal-03845780⟩
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