ABSTRACT
Circulating angiogenic cells (CAC) influence vascular repair through the secretion of proangiogenic factors and cytokines. While CAC are deficient in patients with diabetes and exercise has a beneficial effect on CACs, the impact of these factors on paracrine secretion from CAC is unknown. We aimed to determine whether the in vitro secretion of selected cytokines and nitric oxide (NO) from CAC is influenced by hyperglycemia and acute exercise. Colony-forming unit CAC (CFU-CAC) were cultured from young active men (n = 9, 24 ± 2 years) at rest and after exercise under normal (5 mmol/L) and elevated (15 mmol/L) glucose. Preliminary relative multiplex cytokine analysis revealed that CAC conditioned culture media contained three of six measured cytokines: transforming growth factor-beta-1 (TGFß1), tumor necrosis factor alpha (TNFα), and monocyte chemotactic protein-1 (MCP-1). Single quantitative cytokine analysis was used to determine the concentration of each cytokine from the four conditions. NO was measured via Griess assay. There was a significant effect of CAC exposure to in vivo exercise on in vitro TGFß1 secretion (P = 0.024) that was independent of glucose concentration. There was no effect of glucose or acute exercise on TNFα or MCP-1 concentration (both P > 0.05). The concentration of NO from CFU-CAC cultured in elevated glucose was lower following acute exercise (P = 0.002) suggesting that exercise did not maintain NO secretion under hyperglycemic conditions. Our results identify paracrine signaling factors that may be responsible for the proangiogenic function of CFU-CAC and an influence of acute exercise and elevated glucose on CFU-CAC soluble factor secretion.
Subject(s)
Cytokines/metabolism , Endothelial Cells/metabolism , Exercise/physiology , Glucose/metabolism , Neovascularization, Physiologic/physiology , Colony-Forming Units Assay , Culture Media, Conditioned/pharmacology , Endothelial Cells/cytology , Enzyme-Linked Immunosorbent Assay , Humans , In Vitro Techniques , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Male , Nitric Oxide/metabolism , Paracrine Communication/physiology , Real-Time Polymerase Chain Reaction , Stem Cells/metabolism , Transcriptome , Young AdultABSTRACT
Circulating angiogenic cells (CACs) are a diverse group that have been identified as predictors of cardiovascular health and are inversely proportional to cardiovascular disease (CVD) outcomes. Inactivity is a growing concern in industrialized nations and is an independent risk factor for CVD. There is limited evidence regarding the impact of reduced physical activity (rPA) on different CAC populations. The purpose of this study was to evaluate the effect of objectively monitored rPA with maintained energy balance on two CAC populations (CFU and CD34(+) cells), intracellular nitric oxide (NOi), and genes related to NO production in active, healthy men. Participants (age 25 ± 2.9 yr) refrained from structured physical activity for 10 days, which was reflected by a significant reduction in time in vigorous + very vigorous intensity activity (P = 0.03). Sedentary time tended to increase (P = 0.06) with rPA. CFU CACs have been characterized as mainly monocytic and lymphocytic cells. We found significant reductions in both the number of CFU CACs (-35.69%, P = 0.01) and CFU CAC NOi (-33.84%, P = 0.03). Neither NOi nor the number of CD34(+) cells, which are hematopoietic and endothelial progenitors, changed with rPA. We found no significant differences in NO-related gene expression or oxidative stress-related gene expression with rPA in either CAC type. Therefore, we conclude that although various CAC populations have been related to vascular health, regular physical activity is necessary to maintain CAC NOi and the vulnerability of CACs to short-term reductions in physical activity is population specific.
