The transcriptional coactivator PGC-1alpha mediates exercise-induced angiogenesis in skeletal muscle.

Journal Article (Journal Article)

Peripheral arterial disease (PAD) affects 5 million people in the US and is the primary cause of limb amputations. Exercise remains the single best intervention for PAD, in part thought to be mediated by increases in capillary density. How exercise triggers angiogenesis is not known. PPARgamma coactivator (PGC)-1alpha is a potent transcriptional co-activator that regulates oxidative metabolism in a variety of tissues. We show here that PGC-1alpha mediates exercise-induced angiogenesis. Voluntary exercise induced robust angiogenesis in mouse skeletal muscle. Mice lacking PGC-1alpha in skeletal muscle failed to increase capillary density in response to exercise. Exercise strongly induced expression of PGC-1alpha from an alternate promoter. The induction of PGC-1alpha depended on beta-adrenergic signaling. beta-adrenergic stimulation also induced a broad program of angiogenic factors, including vascular endothelial growth factor (VEGF). This induction required PGC-1alpha. The orphan nuclear receptor ERRalpha mediated the induction of VEGF by PGC-1alpha, and mice lacking ERRalpha also failed to increase vascular density after exercise. These data demonstrate that beta-adrenergic stimulation of a PGC-1alpha/ERRalpha/VEGF axis mediates exercise-induced angiogenesis in skeletal muscle.

Full Text

Duke Authors

Cited Authors

  • Chinsomboon, J; Ruas, J; Gupta, RK; Thom, R; Shoag, J; Rowe, GC; Sawada, N; Raghuram, S; Arany, Z

Published Date

  • December 15, 2009

Published In

Volume / Issue

  • 106 / 50

Start / End Page

  • 21401 - 21406

PubMed ID

  • 19966219

Pubmed Central ID

  • PMC2795492

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.0909131106

Language

  • eng

Conference Location

  • United States