Heterogeneous Circulating Angiogenic Cell Responses to Acute Maximal Exercise.

PURPOSE: Circulating angiogenic cells (CAC) comprise multiple subpopulations of exercise-inducible peripheral blood mononuclear cells (PBMC) that promote angiogenesis and maintain endothelial integrity. We examined the effect of acute maximal exercise on CD31, CD62E, CD14/CD31, CD34/VEGFR2, CD3/CD31, and CD3 PBMC in young, healthy adults. METHODS: Blood samples were collected before and immediately after a graded treadmill exercise test for CAC analysis via flow cytometry. RESULTS: Maximal exercised produced 40%, 29%, 33%, 14%, and 33% increases in lymphocytic CD31, monolymphocytic CD31, CD62E, CD14/CD31, and CD34/VEGFR2 PBMC, respectively (P < 0.05). CD3/CD31 and CD3 cells were not altered with exercise. CD62E and CD14/CD31 PBMC were selectively augmented in women by 54% and 20%, respectively (P < 0.05). Exploratory analyses indicated that maximal exercise induced greater increases in CD62E and CD14/CD31 PBMC among women in the luteal phase compared with those in the follicular phase (P < 0.05). Basal lymphocytic PBMC and postexercise lymphocytic and monolymphocytic CD31 PBMC were lower among contraceptive users than nonusers. CONCLUSIONS: Maximal exercise induces a robust CAC response encompassing both progenitor and nonprogenitor cell types, with these effects differing between men and women for CD62E and CD14/CD31 cell types and the potential influence of menstrual cycle phase and contraceptive use.

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.