Witkowski Sarah, Guhanarayan Gayatri, Burgess Rachel
Department of Kinesiology, University of Massachusetts Amherst, Amherst, Massachusetts
Department of Kinesiology, University of Massachusetts Amherst, Amherst, Massachusetts.
Physiol Rep. 2016 Feb;4(3). doi: 10.14814/phy2.12649. Epub 2016 Feb 4.
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 (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 in vivo exercise on in vitro 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.
循环血管生成细胞（CAC）通过分泌促血管生成因子和细胞因子影响血管修复。虽然糖尿病患者的CAC数量不足，且运动对CAC有有益影响，但这些因素对CAC旁分泌的影响尚不清楚。我们旨在确定高血糖和急性运动是否会影响CAC体外分泌特定细胞因子和一氧化氮（NO）。从年轻活跃男性（n = 9，24±2岁）中分离出集落形成单位CAC（CFU-CAC），在正常（5 mmol/L）和高糖（15 mmol/L）条件下，分别于静息状态和运动后进行培养。初步的相对多重细胞因子分析显示，CAC条件培养基中含有六种检测细胞因子中的三种：转化生长因子-β1（TGFβ1）、肿瘤坏死因子-α（TNFα）和单核细胞趋化蛋白-1（MCP-1）。采用单一细胞因子定量分析来确定四种条件下每种细胞因子的浓度。通过Griess法测定NO。CAC暴露于体内运动对体外TGFβ1分泌有显著影响（P = 0.024），且与葡萄糖浓度无关。葡萄糖或急性运动对TNFα或MCP-1浓度均无影响（P均>0.05）。急性运动后，高糖培养的CFU-CAC中NO浓度降低（P = 0.002），这表明在高血糖条件下运动不能维持NO分泌。我们的研究结果确定了可能负责CFU-CAC促血管生成功能的旁分泌信号因子，以及急性运动和高糖对CFU-CAC可溶性因子分泌的影响。
