PGC-1β regulates angiogenesis in skeletal muscle
Glenn C Rowe1, Cholsoon Jang, Ian S Patten
1Cardiovascular Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
Summary
Peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β) promotes skeletal muscle angiogenesis by increasing vascular endothelial growth factor (VEGF) expression. This finding links oxidative metabolism regulation to vascular density.
Area of Science:
- Molecular biology
- Physiology
- Angiogenesis research
Background:
- Aerobic metabolism relies on oxygen and nutrients delivered by blood vessels.
- Skeletal muscles can adjust blood vessel density to meet metabolic demands.
- Molecular mechanisms coordinating metabolism and vascularization are not fully understood.
Purpose of the Study:
- To investigate the role of peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β) in skeletal muscle angiogenesis.
- To identify molecular pathways regulated by PGC-1β involved in vascularization.
Main Methods:
- Investigated PGC-1β's effect on vascular endothelial growth factor (VEGF) expression in vitro and in vivo.
- Examined the role of estrogen-related receptor-α (ERRα) and hypoxia-inducible factor (HIF) in PGC-1β-mediated VEGF induction.
- Utilized coculture experiments with skeletal myotubes and endothelial cells.
- Generated transgenic mice with skeletal muscle-specific PGC-1β expression.
Main Results:
- PGC-1β induces VEGF expression in skeletal muscle cells and in whole organisms.
- VEGF induction by PGC-1β requires ERRα coactivation and is independent of HIF.
- PGC-1β overexpression in myotubes enhances endothelial cell migration via VEGF signaling.
- Transgenic PGC-1β expression significantly increases skeletal muscle blood vessel density.
Conclusions:
- PGC-1β is a key regulator of angiogenesis in skeletal muscle.
- PGC-1β establishes a novel connection between the regulation of oxidative metabolism and vascular density.
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