Duggan Catherine, Xiao Liren, Wang Ching-Yun, McTiernan Anne
Authors' Affiliation: Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Cancer Epidemiol Biomarkers Prev. 2014 Apr;23(4):648-57. doi: 10.1158/1055-9965.EPI-13-1155. Epub 2014 Feb 5.
Increased physical activity is associated with decreased risk of several types of cancer, but underlying mechanisms are poorly understood. Angiogenesis, in which new blood vessels are formed, is common to adipose tissue formation/remodeling and tumor vascularization.
We examined effects of a 12-month 45 minutes/day, 5 days/week moderate-intensity aerobic exercise intervention on four serum markers of angiogenesis in 173 sedentary, overweight, postmenopausal women, 50 to 75 years, randomized to intervention versus stretching control. Circulating levels of positive regulators of angiogenesis [VEGF, osteopontin (OPN), plasminogen activator inhibitor-1 (PAI-1)], and the negative regulator pigment epithelium-derived factor (PEDF), were measured by immunoassay at baseline and 12 months. Changes were compared using generalized estimating equations, adjusting for baseline levels of analytes and body mass index (BMI).
VEGF, OPN, or PAI-1 levels did not differ by intervention arm. Participants randomized to exercise significantly reduced PEDF (-3.7%) versus controls (+3.0%; P = 0.009). Reductions in fat mass were significantly associated with reductions in PAI-1 (Ptrend = 0.03; Ptrend = 0.02) and PEDF (Ptrend = 0.002; Ptrend = 0.01) compared with controls, or to those who gained any fat mass respectively. There was a significant association between decreases in VO2max, and increased reductions in PEDF (Ptrend = 0.03), compared with participants who increased their level of fitness.
Fat loss reduces circulating PAI-1 and PEDF. Changes in VO2max are associated with alterations in PEDF, but these associations are complex.
Unexpected reductions in PEDF with decreasing fat mass, and with decreasing VO2max, warrant further study, including examining the effects of different types and intensities of exercise; and role of dietary weight-loss with and without exercise.
增加体力活动与多种癌症风险降低相关，但潜在机制尚不清楚。血管生成，即新血管形成，在脂肪组织形成/重塑和肿瘤血管化过程中均常见。
我们对173名年龄在50至75岁、久坐、超重的绝经后女性进行了一项为期12个月、每天45分钟、每周5天的中等强度有氧运动干预，将其随机分为干预组和伸展对照组，研究该干预对四种血管生成血清标志物的影响。通过免疫测定法在基线和12个月时测量血管生成正调节因子[血管内皮生长因子（VEGF）、骨桥蛋白（OPN）、纤溶酶原激活物抑制剂-1（PAI-1）]以及负调节因子色素上皮衍生因子（PEDF）的循环水平。使用广义估计方程比较变化，并对分析物的基线水平和体重指数（BMI）进行调整。
VEGF、OPN或PAI-1水平在干预组之间没有差异。随机分配到运动组的参与者与对照组相比，PEDF显著降低（-3.7%对+3.0%；P = 0.009）。与对照组相比，或与那些有脂肪增加的人相比，脂肪量的减少分别与PAI-1（Ptrend = 0.03；Ptrend = 0.02）和PEDF（Ptrend = 0.002；Ptrend = 0.01）的降低显著相关。与体能水平提高的参与者相比，最大摄氧量（VO2max）的降低与PEDF更大程度的降低之间存在显著关联（Ptrend = 0.03）。
脂肪减少会降低循环中的PAI-1和PEDF。VO2max的变化与PEDF的改变相关，但这些关联很复杂。
随着脂肪量减少和VO2max降低，PEDF意外降低，这值得进一步研究，包括研究不同类型和强度运动的影响；以及饮食减肥在有运动和无运动情况下的作用。
