Angiogenesis in Skeletal Muscle

Abstract

Growth of vessels in normal adult skeletal muscles occurs during development, cold exposure, increased activity, administration of certain hormones, and increased physical activity (such as endurance exercise or chronic electrical stimulation). It always starts as growth of capillaries, with growth of larger vessels following later, or sometimes not at all: in endurance training growth of capillaries is not accompanied by growth of larger vessels, while a long-term increase in activity due to electrical stimulation leads to growth of the whole vascular bed (demonstrated by increased capillarization, corrosion casts, number of arterioles and maximal conductance measurements. One factor involved in capillary growth in stimulated muscles is the greater shear stress accompanying an increased velocity of flow, as similar growth was found in animals where long-term increase in blood flow was induced by the alpha1 blocker prazosin. Increased shear stress damaged the luminal glycocalyx and also caused a release of prostaglandins. These appear to mediate capillary growth as simultaneous administration of indomethacin decreased incorporation of bromodeoxyuridine into capillary-linked nuclei and attenuated capillary growth. In addition, distortion of the capillary basement membrane by increased capillary wall tension, and by continuous stretching and relaxation of surrounding muscle fibres,may also involved. Long-term muscle stretch due to extirpation of agonists induced capillary growth, but without an increase in blood flow. Disturbance of the basement membrane may lead to release of growth factors. While the evidence for the involvement of bFGF was negative, a low molecular weight angiogenic factor (ESAF) was demonstrated in both stimulated and stretched muscles. Capillary growth in stimulated muscles may also be enhanced by pericyte withdrawal as there was significantly less of capillary perimeter covered by pericytes in muscles with demonstrated capillary growth. Thus mechanical factors acting both from luminal and abluminal side can initiate capillary growth in skeletal muscle by activating either prostaglandins, ESAF or possibly other growth factors, but not bFGF.