What makes vessels grow with exercise training?

Abstract

Exercise and muscle contractions create a powerful stimulus for structural remodeling of the vasculature. An increase in flow velocity through a vessel increases shear stress, a major stimulus for enlargement of conduit vessels. This leads to an endothelial-dependent, nitric oxide-dependent enlargement of the vessel. Increased flow within muscle, in the absence of contractions, leads to an enhanced capillarity by intussusceptive angiogenesis, a process of capillary splitting by intraluminal longitudinal divide. In contrast, sprouting angiogenesis requires extensive endothelial cell proliferation, with degradation of the extracellular matrix to permit migration and tube formation. This occurs during muscle adaptations to chronic contractions and/or muscle overload. The angiogenic growth factor VEGF appears to be an important element in angiogenesis. Recent advances in research have identified hemodynamic and mechanical stimuli that upregulate angiogenic processes, demonstrated a complexity of potent growth factors and interactions with their corresponding receptors, detected an interaction of cellular signaling events, and identified important tissue reorganization processes that must be coordinated to effect vascular remodeling. It is likely that much of this information is applicable to the vascular remodeling that occurs in response to exercise and/or muscle contractions.

Shear stress‐induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible

“…2004), including signals effective over different time courses such as altered enzymatic activity (Mujika & Padilla 2001) and mechanical stretch (Prior et al . 2004, Williams et al . 2006a).…”

“…While VEGF expression decreases following prazosin‐induced chronic hyperaemia, it rises during acute increases in blood flow associated with periods of activity (Prior et al . 2004). During periods of disuse, regression of capillaries is associated with muscle atrophy (Dedkov et al .…”

“…Vasoactive metabolites mediate arteriolar vasodilatation, and the accompanying increase in vascular conductance is a major stimulus for exercise‐induced angiogenesis (Prior et al . 2004). As capillaries have low compliance, elevated microvascular perfusion leads to an elevated capillary shear stress, as confirmed by intravital microscopy observations (Hudlická et al .…”

Multi-scale Computational Models of Pro-angiogenic Treatments in Peripheral Arterial Disease

“…Although the exact relationship has not been experimentally measured, we used experimental data on the dependence of VEGF release on HIF1a and O 2 26,29,48,59 to formulate an empirical relationship between oxygen tension (averaged across the myocyte cross section) and local VEGF release. 32 Non-exercise trained rats do not increase VEGF secretion in response to hypoxia 29,40,47 but exercise-trained rats do, 29,59 and based on experimental data, 26,59 we assume that the maximum hypoxia-induced secretion increase is six times the level of VEGF secretion in normoxia. 24,32 VEGF Transport and VEGF-receptor Binding VEGF released by the myocyte into the interstitial space diffuses and (in the case of VEGF 164 ) can be (2) and NRP1 (N).…”

“…33,34 The most common animal model of PAD is surgical ligation of the femoral or iliac arteries. 3,29,44,47,51,53 Although this does not completely reproduce the symptoms of PAD, it has become a valuable tool and a useful correlation. Thus, the simulations we present here are for rat EDL muscle following femoral ligation.…”