The effect of exercise on blood concentrations of angiogenesis markers in older adults: a systematic review and meta-analysis

Background: Physical exercise benefits health and can improve angiogenesis—often impaired with aging—but mechanisms remain unclear. This systematic review and meta-analysis examined the effects of exercise on peripheral angiogenesis markers in older adults. Methods: MEDLINE, Embase, and Cochrane CENTRAL were searched (English, March 10, 2022) for peer-reviewed studies reporting serum, plasma, or blood concentrations of angiogenesis proteins before and after at least moderate-intensity exercise interventions in adults with mean age ≥50 years. Risk of bias was assessed with standardized criteria. Random-effects meta-analyses generated standardized mean differences (SMD) with 95% confidence intervals (CI). Publication bias was assessed with Egger’s test, funnel plots, and trim-and-fill; subgroup analyses and meta-regressions explored heterogeneity. Results: Forty-four articles met inclusion; 38 contributed to meta-analyses of five proteins. Vascular endothelial growth factor (VEGF) increased after exercise (SMD [95% CI] = 0.18 [0.03, 0.34], p = 0.02), while E-selectin (CD62E) decreased (SMD [95% CI] = −0.72 [−1.42, −0.03], p = 0.04). Endostatin (SMD [95% CI] = 0.28 [−0.56, 1.11], p = 0.5), fibroblast growth factor 2 (FGF2; SMD [95% CI] = 0.03 [−0.18, 0.23], p = 0.8), and matrix metallopeptidase-9 (MMP9; SMD [95% CI] = −0.26 [−0.97, 0.45], p = 0.5) showed no significant changes. Conclusions: Among five angiogenesis blood markers, only VEGF and CD62E changed with exercise in older adults. These biomarker shifts may partially explain exercise-related benefits on angiogenesis and health, warranting further study.