Effect of acute exercise on circulating angiogenic cell and microparticle populations

Subpopulations of peripheral blood mononuclear cells (PMBCs), known as circulating angiogenic cells (CACs), have been implicated in endothelial repair, angiogenesis and vascular homeostasis. Conversely, microparticles released from endothelial cells, platelets and leucocytes in response to injury or apoptosis are elevated in chronic diseases. We investigated the effect of acute exercise on CAC subpopulations, specifically CD34(+)/VEGFR2(+), CD3(+)/CD31(+), CD14(+)/CD31(+) and CD62E(+) PBMCs and CD62E(+), CD31(+)/CD42b(-) and CD34(+) MPs in men and women. Additionally, we examined angiogenesis-related gene expression in CD34(+), CD31(+) and CD62E(+) PBMCs at baseline and after exercise. Finally, we examined whether acute exercise modulates CD62E(+) PBMC paracrine actions on cultured endothelial cells. Blood samples for CAC and MP analyses were obtained before and after cycling exercise at 70% peak oxygen uptake that elicited an energy expenditure of 600 kcal. Exercise produced a decrease in CD14(+)/CD31(+) PBMCs, whereas CD62E expression on PBMCs increased with exercise. CD34(+)/VEGFR2(+) and CD3(+)/CD31(+) PBMC levels were not altered with exercise. Gene expression analysis revealed a more proangiogenic phenotype in CD62E(+) cells at baseline compared with CD31(+) and CD34(+) cells. Conditioned media from CD62E(+) PBMCs obtained after exercise exerted a proangiogenic influence on human umbilical vein endothelial cells, with increases in genes encoding receptors for growth factors (KDR, FGFR1 and EGFR) and inflammatory mediators (TLR4 and TNFR1). Finally, exercise increased CD62E(+) endothelial MPs in men and increased CD34(+) MPs in women. Our work highlights the potential role of CD62E(+) cells as a novel, exercise-responsive proangiogenic cell population and demonstrates sex-specific exercise-induced changes in circulating MPs.