Effect of a 12-Month Exercise Intervention on Serum Biomarkers of Angiogenesis in Postmenopausal Women: A Randomized Controlled Trial

Abstract

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.