AMPK regulates basal skeletal muscle capillarization and VEGF expression, but is not necessary for the angiogenic response to exercise

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dc.contributor.authorZwetsloot, Kevin A.en_US
dc.contributor.authorWesterkamp, Lenna M.en_US
dc.contributor.authorHolmes, Burton F.en_US
dc.contributor.authorGavin, Timothy Patricken_US
dc.date.accessioned2011-01-27T15:30:09Zen_US
dc.date.accessioned2011-05-16T20:40:46Z
dc.date.available2011-01-27T15:30:09Zen_US
dc.date.available2011-05-16T20:40:46Z
dc.date.issued2008-12-15en_US
dc.description.abstract5 -AMP-activated protein kinase(AMPK)is a metabolic fuel sensor that monitors cellular energy charge, while the vasculature is important for maintaining cellular energy homeostasis. Mice with muscle-specific inactive AMPK (AMPK DN) were used to investigate if AMPK regulates skeletal muscle capillarization and the angiogenic responses to exercise. Two hours of the AMP analogueAICAR(1.0 g kg - 1)or systemichypoxia (6%O2) increased vascular endothelial growth factor (VEGF) mRNA in wild-type (WT), but not in AMPK DN mice. In contrast, the increase in VEGF mRNA with acute exercise (1 h at 20m min - 1, 10% gradient) was greater in AMPK DN compared to WT mice. Nuclear run-on assay demonstrated that exercise increased VEGF transcription, while hypoxia decreased VEGF transcription. There was no difference in VEGF transcription between WT and AMPK DN. There was a strong correlation between VEGF transcription and VEGF mRNA at rest and with exercise. Resting capillarization was lower in AMPK DN compared to WT. Wheel running (28 days) increased capillarization and this response was AMPK independent. Significant correlations between VEGF protein and muscle capillarization are consistent with VEGF being an important determinant of skeletal muscle capillarization. These data are to our knowledge the first to demonstrate in skeletal muscle in vivo that: (1) AMPK is necessary for hypoxia-induced VEGF mRNA stabilization, (2) acute exercise increases VEGF transcription, (3) inhibition of AMPK augments the VEGF mRNA response to acute exercise, and (4) AMPK regulates basal VEGF expression and capillarization, but is not necessary for exercise-induced angiogenesis. Originally published Journal of Physiology, Vol. 586, No. 24, Dec 2008en_US
dc.identifier.citationJournal of Physiology; 586:24 p. 6021-6035en_US
dc.identifier.doi10.1113/jphysiol.2008.159871
dc.identifier.pmidPMC2655430en_US
dc.identifier.urihttp://hdl.handle.net/10342/3098en_US
dc.language.isoen_USen_US
dc.publisherEast Carolina Universityen_US
dc.publisherEast Carolina Universityen_US
dc.relation.urihttp://jp.physoc.org/content/586/24/6021en_US
dc.rightsAuthor notified of opt-out rights by Cammie Jennings prior to upload of this article.en_US
dc.subjectAMPKen_US
dc.subjectSkeletal muscle capillarizationen_US
dc.subjectVascular endothelial growth factoren_US
dc.titleAMPK regulates basal skeletal muscle capillarization and VEGF expression, but is not necessary for the angiogenic response to exerciseen_US
dc.typeArticleen_US
ecu.journal.issue24
ecu.journal.nameJournal of Physiology
ecu.journal.pages6021-6035
ecu.journal.volume586

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