Exercise‐Induced Capillary Growth in Human Skeletal Muscle and the Dynamics of VEGF

Abstract

In skeletal muscle, growth of capillaries is an important adaptation to exercise training that secures adequate diffusion capacity for oxygen and nutrients even at high-intensity exercise when increases in muscle blood flow are profound. Mechanical forces present during muscle activity, such as shear stress and passive stretch, lead to cellular signaling, enhanced expression of angiogenic factors, and initiation of capillary growth. The most central angiogenic factor in skeletal muscle capillary growth is VEGF. During muscle contraction, VEGF increases in the muscle interstitium, acts on VEGF receptors on the capillary endothelium, and thereby stimulates angiogenic processes. A primary source of muscle interstitial VEGF during exercise is the skeletal muscle fibers which contain large stores of VEGF within vesicles. We propose that, during muscle activity, these VEGF-containing vesicles are redistributed toward the sarcolemma where the contents are secreted into the extracellular fluid. VEGF mRNA expression is increased primarily after exercise, which allows for a more rapid replenishment of VEGF stores lost through secretion during exercise. Future studies should focus on elucidating mechanisms and regulation of VEGF secretion.

Peak oxygen uptake and self‐reported physical health are strong predictors of long‐term survival after heart transplantation

“…VEGF is dominantly secreted by working skeletal muscles, an essential factor to increase capillary density, oxygen delivery and thereby exercise performance (109)(110)(111). Based on our previous results showing improved muscular exercise capacity after HIT (30), and now the finding of an increased VEGF response, we suggest that this mechanism is of high importance also in the HTx recipients.…”

Morinda citrifolia leaf enhanced performance by improving angiogenesis, mitochondrial biogenesis, antioxidant, anti-inflammatory & stress responses

“…VEGF is the main angiogenic factor in skeletal muscle capillary growth, and is stimulated by mechanical forces during muscle activity (shear stress and stretch) (Hoier & Hellsten, 2014). The skeletal muscle fibers contain large stores of VEGF within vesicles, and during exercise, these vesicles are secreted into the extracellular fluid (Hoier & Hellsten, 2014).…”

Cardiovascular Adaptations to Exercise Training

“…They showed that eight weeks of moderate intensity cycle training in sedentary healthy young males, lead to an approximate 40% increase in capillary density in the thigh muscle (8). In general, the literature shows that, when previously sedentary, healthy individuals are subjected to periods of 4 to 8 weeks of endurance training of moderate intensities at between 60% and 80% of VO 2max , an increase in capillarization of between 10% and 40% is observed (190,206,232) (Fig. 8).…”