Intense intermittent exercise provides weak stimulus for vascular endothelial growth factor secretion and capillary growth in skeletal muscle

Abstract

New Findings r What is the central question of this study?Does intense intermittent exercise provide a sufficient angiogenic stimulus to induce capillary growth in skeletal muscle conditioned by moderate intensity exercise training? r What is the main finding and its importance?We show that higher levels of shear stress and metabolism associated with intense exercise do not provide further stimulus for capillary growth. Instead, secretion of vascular endothelial growth factor and proliferation of endothelial cells are lower in response to intense compared with moderate-intensity exercise, suggesting that intense exercise is a weaker stimulus for angiogenesis. The data provide novel insight into the regulation of vascular endothelial growth factor secretion in muscle and the role of pro-angiogenic and angiostatic factors.The effect of acute intense intermittent exercise compared with moderate-intensity exercise on angiogenic factors and the effect of 4 weeks of intense intermittent training on capillary growth were examined in nine healthy young men, preconditioned by moderate-intensity endurance training. The intense training consisted of 24 bouts of 1 min cycling at an initial work rate of 316 ± 19 W (∼117% of pretraining maximal oxygen uptake), performed three times per week. Skeletal muscle biopsies and muscle microdialysates were otained from the vastus lateralis before, during and after acute exercise performed at either moderate or high intensity. Comparison of the response in angiogenic factors to acute moderate-versus high-intensity exercise, performed prior to the intense training intervention, revealed that intense exercise resulted in a markedly lower (∼60%; P < 0.05) increase in interstitial vascular endothelial growth factor than did moderateintensity exercise. Muscle interstitial fluid obtained during moderate-intensity exercise increased endothelial cell proliferation in vitro more than interstitial fluid obtained during intense exercise (sixfold versus 2.5-fold, respectively; P < 0.05). The 4 weeks of high-intensity training did not lead to an increased capillarization in the muscle but abolished the exercise-induced increase in mRNA for several angiogenic factors, increased the protein levels of endothelial nitric oxide synthase, lowered the protein levels of thrombospondin-1 in muscle but increased the interstitial protein levels of thrombospondin-1. We conclude that intense intermittent exercise provides a weak stimulus for vascular endothelial growth factor secretion and endothelial cell proliferation

Training for skeletal muscle capillarization: a Janus-faced role of exercise intensity?

“…Moreover, peroxisome proliferator-activated γ-receptor co-activator (PGC-1α), an important regulator of both angiogenesis and mitochondrial biogenesis, was also increased to the same extent in the two training protocols. These findings are interesting, because activation of PGC-1α and subsequent mitochondrial biogenesis is largely intensity dependent (Oliveira et al 2014), whereas angiogenesis appears to be hampered when intensity gets too high (Høier et al 2013). As such, recent reports have shown that increasing the number of all-out efforts while reducing total training volume has a negative impact on skeletal muscle VEGF levels and ultimately capillarization (Gliemann et al 2015).…”

“…As such, recent reports have shown that increasing the number of all-out efforts while reducing total training volume has a negative impact on skeletal muscle VEGF levels and ultimately capillarization (Gliemann et al 2015). Specifically, it has been shown that the angiogenic potency of an interval-based training session is less than that of a continuous moderate-intensity training session (Høier et al 2013). This has been shown over the past few years in various sports, including running, cycling, and soccer, and in both untrained, moderately trained, and elite athletes.…”

“…Second, as intensity goes up, so does the release of anti-angiogenic factors. These are released to keep capillary growth from going haywire, and it has been shown that at least some of these are upregulated more after high intensity compared to moderate-intensity exercise (Høier et al 2013). Finally, or maybe ultimately, the aerobic component of 4 × 30 s all-out exercise is rather limited compared to the energy turnover from anaerobic processes (Beneke et al 2002).…”

Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men

“…Immunohistochemistry was performed as previously described in detail (23). Briefly, sections were rinsed and incubated with a primary antibody against CD-31 (endothelial cell marker, M0822, DakoCytomation, Glostrup, Denmark) and myosin heavy chain (MHC) antibodies against MHC I (M8421, Sigma, St. Louis, MO) and MHC IIa (N2.261, Developmental Studies Hybridoma Bank, University of Iowa).…”

“…TIMP-1 inhibits degradation of the extracellular matrix by inhibiting matrix metalloproteinases (MMPs) and may thereby limit capillary growth (3,62). The expression of TIMP-1 in skeletal muscle is sensitive to muscle activity where acute exercise transiently increases TIMP-1 mRNA levels (23) and endurance training leads to elevated TIMP-1 protein content (21).…”