Effect of hypoxia-inducible factor 1 on vascular endothelial growth factor expression in exercised human skeletal muscle: a systematic review and meta-analysis

Within contracting human skeletal muscle (SKM), oxygen pressure significantly drops, which has been linked to the activation of a signaling cascade mediated by hypoxia-inducible factor 1a (HIF-1a). This cascade leads to SKM angiogenesis through vascular endothelial growth factor (VEGF). However, the...

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Detalhes bibliográficos
Autores: Aragón Vela, Jerónimo, Casuso Pérez, Rafael
Formato: artículo
Fecha de publicación:2025
País:España
Recursos:Universidad Loyola Andalucía
Repositorio:Brújula
OAI Identifier:oai:repositorio.uloyola.es:20.500.12412/6743
Acesso em linha:https://hdl.handle.net/20.500.12412/6743
Access Level:acceso abierto
Palavra-chave:Angiogenesis
HIF-1
Hypoxia
Training
VEGF
Descrição
Resumo:Within contracting human skeletal muscle (SKM), oxygen pressure significantly drops, which has been linked to the activation of a signaling cascade mediated by hypoxia-inducible factor 1a (HIF-1a). This cascade leads to SKM angiogenesis through vascular endothelial growth factor (VEGF). However, the role of HIF-1a in exercise-induced VEGF expression within SKM remains unclear. In this study, we systematically reviewed the literature to quantitatively synthesize all available evidence on HIF-1a activation in exercised human muscle. We identified 21 studies providing 39 effect sizes of pre- and postexercise SKM HIF-1a data from 235 subjects, with 15 of them also presenting data on VEGF mRNA levels. HIF-1a mRNA increased in response to high-intensity and resistance exercise, regardless of participants’ physical fitness levels. Notably, meta-regression showed that exercise-induced VEGF expression is not modulated by HIF-1a mRNA levels. Similarly, when plotting exercise-induced fold changes of VEGF and HIF-1a, no significant relationship was observed. Our findings demonstrate that HIF-1a is expressed in contracting SKM. However, the role of HIF-1a in the exercise-induced angiogenic response remains unclear, as most of the available evidence is limited to transcriptional data. NEW & NOTEWORTHY This analysis shows that both HIF-1a mRNA and protein levels are significantly elevated in skeletal muscle following dynamic exercise. However, the absence of a clear relationship between HIF-1a mRNA and the mRNA levels of its downstream target VEGF suggests that HIF-1a mRNA expression alone may not reliably reflect its regulatory role in VEGF transcription in response to exercise. Given the limited number of human studies examining posttranslational regulation of HIF-1a, its precise contribution to VEGF-mediated angiogenic signaling in exercised skeletal muscle remains uncertain.