Effect of hypoxia-inducible factor 1 on vascular endothelial growth factor expression in exercised human skeletal muscle: a systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of human pre-post exercise studies (by design analogy)
PubMed 40522862 · doi:10.1152/ajpcell.00297.2025
What was done
Systematic review and meta-analysis investigating hypoxia-inducible factor 1α (HIF-1α) activation and its association with vascular endothelial growth factor (VEGF) expression in exercised human skeletal muscle. The authors analyzed 21 studies reporting 39 effect sizes of pre- and post-exercise HIF-1α measurements across 235 subjects, including 15 studies that also measured VEGF mRNA. Meta-regression and fold-change analyses evaluated the relationship between exercise-induced HIF-1α and VEGF expression across exercise modalities and physical fitness levels.
What was found
HIF-1α mRNA increased following high-intensity and resistance exercise, independent of fitness status. Dynamic exercise also elevated HIF-1α protein levels. However, meta-regression indicated that exercise-induced VEGF expression was not modulated by HIF-1α mRNA levels, and no significant relationship was observed between exercise-induced fold changes in VEGF and HIF-1α. The abstract reports no exact effect sizes, variance estimates, or p-values.
Why it matters
These findings indicate that while exercise stimulates skeletal muscle HIF-1α, HIF-1α mRNA levels alone do not account for downstream VEGF expression in humans. This highlights that transcript-level measurements are insufficient to capture HIF-1α-mediated angiogenic regulation in exercised muscle.
Limits
The abstract provides no numerical effect estimates or confidence intervals. The underlying evidence base is largely restricted to transcriptional (mRNA) data rather than post-translational regulation or active protein dynamics. Total sample size across 21 studies is modest (235 participants), encompassing diverse exercise protocols.
Cited by
- supports Changes in blood oxygenation trigger hypoxia-inducible factor 1-alpha (HIF-1a), which enhances transcription of vascular endothelial growth factor (VEGF) to promote blood vessel growth.