Increased plasma levels of soluble vascular endothelial growth factor receptor 1 (sFlt-1) in women by moderate exercise and increased plasma levels of vascular endothelial growth factor in overweight/obese women

Abstract

The incidence of breast cancer is increasing worldwide, and this seems to be related to an increase in lifestyle risk factors, including physical inactivity, and overweight/obesity. We previously reported that exercise induced a circulating angiostatic phenotype characterized by increased sFlt-1 and endostatin and decreased unbound-VEGF in men. However, there is no data on women. The present study determines the following: 1) whether moderate exercise increased sFlt-1 and endostatin and decreased unbound-VEGF in the circulation of adult female volunteers; 2) whether overweight/obese women have a higher plasma level of unbound-VEGF than lean women. 72 African American and Caucasian adult women volunteers aged from 18–44 were enrolled into the exercise study. All the participants walked on a treadmill for 30 minutes at a moderate intensity (55–59% heart rate reserve), and oxygen consumption (VO2) was quantified by utilizing a metabolic cart. We had the blood samples before and immediately after exercise from 63 participants. ELISA assays (R&D Systems) showed that plasma levels of sFlt-1 were 67.8±3.7 pg/ml immediately after exercise (30 minutes), significantly higher than basal levels, 54.5±3.3 pg/ml, before exercise (P < 0.01; n=63). There was no significant difference in the % increase of sFlt-1 levels after exercise between African American and Caucasian (P=0.533) or between lean and overweight/obese women (P=0.892). There was no significant difference in plasma levels of unbound VEGF (35.28±5.47 vs. 35.23±4.96 pg/ml; P=0.99) or endostatin (111.12±5.48 vs. 115.45±7.15 ng/ml; P=0.63) before and after exercise. Basal plasma levels of unbound-VEGF in overweight/obese women were 52.26±9.6 pg/ml, significantly higher than basal levels of unbound-VEGF in lean women, 27.34±4.99 pg/ml (P < 0.05). The results support our hypothesis that exercise-induced plasma levels of sFlt-1 could be an important clinical biomarker to explore the mechanisms of exercise training in reducing breast cancer progression and that VEGF is an important biomarker in obesity and obesity-related cancer progression.

Dietary Weight Loss and Exercise Effects on Serum Biomarkers of Angiogenesis in Overweight Postmenopausal Women: A Randomized Controlled Trial

“…While some studies have also reported effects of exercise and weight-loss on these angiogenic factors,(39,40) the studies have been small,(41,42) cross-sectional,(43) or limited to men. (44) In one study, 79 participants were randomized to a 12-week trial comparing an exercise intervention, a hypocaloric diet, and a combined arm, found that VEGF-A was non-significantly reduced by 10-22% in the weight-loss groups.…”

Multifaceted Leptin Network: The Molecular Connection Between Obesity and Breast Cancer

“…VEGF is considered an adipokine due to its synthesis in adipose tissue and is positively correlated with increased BMI [76]. High circulating levels and increased tumoral expression of VEGF is associated with poor prognosis [77,78]. Recent studies have shown that leptin is a pro-angiogenic cytokine promoting angiogenesis, upregulating VEGF and VEGF receptors in breast cancer.…”

Exercise increases serum endostatin levels in female and male patients with diabetes and controls

“…Brixius et al stated a decrease of endostatin plasma levels in 50–60 year old male overweight and untrained men after 6 months of moderate exercise 3 times/week [26]. However, Makey et al [27] did not find an exercise-induced increase of endostatin in overweight/obese women, but in this study the participants “only” walked on a treadmill at moderate intensity. Nevertheless, considering the results of the mentioned studies both unique and regular physical exercise seems to have an impact on endostatin levels in healthy individuals, where endostatin seems to increase during exercise and to decrease after regular sportive activity.…”