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 invitro 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±2years) at rest and after exercise under normal (5mmol/L) and elevated (15mmol/L) glucose. Preliminary relative multiplex cytokine analysis revealed that CAC conditioned culture media contained three of six measured cytokines: transforming growth factor-beta-1 (TGFβ1), 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 invivo exercise on invitro TGFβ1 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.
Highlights
Vascular regenerative cell types including circulating angiogenic cells (CAC) support vessel remodeling via differentiation into endothelial cells and/or the secretion of paracrine factors (Sahoo et al 2011; Hynes et al 2013; Landers-Ramos et al 2015) and have been identified via cell surface markers (e.g., CD34, VEGFR2, CD133) and characteristics (Rehman et al 2003; Urbich et al 2005)
Colonyforming unit CAC (CFU-CAC) are related to endothelial function measured via flow-mediated brachial reactivity and conventional cardiovascular disease (CVD) risk factors (Hill et al 2003)
The purpose of this study was to evaluate whether elevated glucose levels similar to those found in patients with poorly controlled diabetes, would influence the release of nitric oxide (NO) and cytokine signaling factors from colony-forming units (CFU)-CAC in vitro and whether an acute bout of exercise altered this response
Summary
Vascular regenerative cell types including circulating angiogenic cells (CAC) support vessel remodeling via differentiation into endothelial cells and/or the secretion of paracrine factors (Sahoo et al 2011; Hynes et al 2013; Landers-Ramos et al 2015) and have been identified via cell surface markers (e.g., CD34, VEGFR2, CD133) and characteristics (e.g., colony formation and acetylated LDL uptake) (Rehman et al 2003; Urbich et al 2005). Colony-forming CAC are recognized as a mixed cell population that consist largely of hematopoietic cells including monocytes and lymphocytes in addition to CD34+ endothelial progenitors (Rohde et al 2006; Yoder et al 2007). CFU-CAC are related to endothelial function measured via flow-mediated brachial reactivity and conventional cardiovascular disease (CVD) risk factors (Hill et al 2003). One explanation for this relationship is that the complement of cells that comprise CFU-CAC secrete factors to influence endothelial cell function (Rohde et al 2006, 2007; Pula et al 2009).
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