TY - JOUR

T1 - Hormetic modulation of angiogenic factors by exercise-induced mechanical and metabolic stress in human skeletal muscle

AU - Fiorenza, Matteo

AU - Gliemann, Lasse

AU - Brandt, Nina

AU - Bangsbo, Jens

N1 - CURIS 2020 NEXS 307

PY - 2020

Y1 - 2020

N2 - This study used an integrative experimental model in humans to investigate whether muscle angiogenic factors are differentially modulated by exercise stimuli eliciting different degrees of mechanical and metabolic stress. In a randomized crossover design, twelve men performed two low‑volume high-intensity exercise regimens, including short sprint intervals (SSI) or long sprint intervals (LSI) inducing pronounced mechanical/metabolic stress, and a high‑volume moderate‑intensity continuous exercise protocol (MIC) inducing mild but prolonged mechanical/metabolic stress. Gene and protein expression of angioregulatory factors was determined in vastus lateralis muscle samples obtained before and after exercise. Exercise upregulated muscle VEGF mRNA to a greater extent in LSI and MIC compared to SSI. Analysis of angioregulatory factors sensitive to shear stress revealed more marked exercise-induced VEGF‑R2 mRNA responses in MIC than SSI, as well as greater PECAM‑1 and eNOS mRNA responses in LSI than SSI. No apparent exercise‑induced phosphorylation of shear stress‑sensory proteins VEGF‑R2Tyr1175, PECAM‑1Tyr713 and eNOSSer1177 was observed despite robust elevations in femoral artery shear stress. Exercise evoked greater mRNA responses of the mechanical stretch sensor MMP9 in SSI than MIC. Exercise‑induced mRNA responses of the metabolic stress sensor HIF‑1α were more profound in LSI than SSI. These results suggest that low-volume high-intensity exercise transcriptionally activates angiogenic factors in a mechanical/metabolic stress‑dependent manner. Furthermore, the angiogenic potency of low-volume high-intensity exercise appears similar to that of high‑volume moderate‑intensity exercise, but only on condition of eliciting severe mechanical/metabolic stress. We conclude that the angiogenic stimulus produced by exercise depends on both magnitude and protraction of myocellular homeostatic perturbations.

AB - This study used an integrative experimental model in humans to investigate whether muscle angiogenic factors are differentially modulated by exercise stimuli eliciting different degrees of mechanical and metabolic stress. In a randomized crossover design, twelve men performed two low‑volume high-intensity exercise regimens, including short sprint intervals (SSI) or long sprint intervals (LSI) inducing pronounced mechanical/metabolic stress, and a high‑volume moderate‑intensity continuous exercise protocol (MIC) inducing mild but prolonged mechanical/metabolic stress. Gene and protein expression of angioregulatory factors was determined in vastus lateralis muscle samples obtained before and after exercise. Exercise upregulated muscle VEGF mRNA to a greater extent in LSI and MIC compared to SSI. Analysis of angioregulatory factors sensitive to shear stress revealed more marked exercise-induced VEGF‑R2 mRNA responses in MIC than SSI, as well as greater PECAM‑1 and eNOS mRNA responses in LSI than SSI. No apparent exercise‑induced phosphorylation of shear stress‑sensory proteins VEGF‑R2Tyr1175, PECAM‑1Tyr713 and eNOSSer1177 was observed despite robust elevations in femoral artery shear stress. Exercise evoked greater mRNA responses of the mechanical stretch sensor MMP9 in SSI than MIC. Exercise‑induced mRNA responses of the metabolic stress sensor HIF‑1α were more profound in LSI than SSI. These results suggest that low-volume high-intensity exercise transcriptionally activates angiogenic factors in a mechanical/metabolic stress‑dependent manner. Furthermore, the angiogenic potency of low-volume high-intensity exercise appears similar to that of high‑volume moderate‑intensity exercise, but only on condition of eliciting severe mechanical/metabolic stress. We conclude that the angiogenic stimulus produced by exercise depends on both magnitude and protraction of myocellular homeostatic perturbations.

KW - Faculty of Science

KW - Angiogenesis

KW - Vascular endothelial grow factor

KW - Endothelial nitric oxide synthase

KW - Hypoxia inducible factor

KW - High-intensity interval training (HIIT)

U2 - 10.1152/ajpheart.00432.2020

DO - 10.1152/ajpheart.00432.2020

M3 - Journal article

C2 - 32822216

VL - 319

SP - H824-H834

JO - American Journal of Physiology: Heart and Circulatory Physiology

JF - American Journal of Physiology: Heart and Circulatory Physiology

SN - 0363-6135

IS - 4

ER -