Alteration in angiogenic and anti-angiogenic forms of vascular endothelial growth factor-A in skeletal muscle of patients with intermittent claudication following exercise training

• Published in: Vascular medicine (London, England) England), 2012-04, Vol.17 (2), p.94-100
• Main Authors: Jones, W Schuyler, Duscha, Brian D, Robbins, Jennifer L, Duggan, Natasha N, Regensteiner, Judith G, Kraus, William E, Hiatt, William R, Dokun, Ayotunde O, Annex, Brian H
• Format: Article
• Language: English
• Subjects: Aged; Analysis of Variance; Biological and medical sciences; Biopsy; Blood and lymphatic vessels; Capillaries - physiopathology; Cardiology. Vascular system; Cardiovascular system; Colorado; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Enzyme-Linked Immunosorbent Assay; Exercise Therapy; Exercise Tolerance; Female; Humans; Intermittent Claudication - etiology; Intermittent Claudication - metabolism; Intermittent Claudication - physiopathology; Intermittent Claudication - therapy; Male; Medical sciences; Middle Aged; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Neovascularization, Physiologic; North Carolina; Peripheral Arterial Disease - complications; Peripheral Arterial Disease - metabolism; Peripheral Arterial Disease - physiopathology; Peripheral Arterial Disease - therapy; Pharmacology. Drug treatments; Recovery of Function; Time Factors; Treatment Outcome; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-1 - metabolism; Vasodilator agents. Cerebral vasodilators
• ISSN: 1358-863X; 1477-0377
• DOI: 10.1177/1358863X11436334

The aims of this study were twofold: (1) to identify whether peripheral artery disease (PAD) patients had increased muscle concentration of angiogenic VEGF-A, anti-angiogenic VEGF165b or VEGF receptor 1 (VEGF-R1) when compared with control subjects, and (2) to evaluate whether exercise training in PAD patients was associated with changes in muscle concentration of VEGF-A, VEGF165b or VEGF-R1. At baseline, 22 PAD and 30 control subjects underwent gastrocnemius muscle biopsy. Twelve PAD patients were treated with supervised exercise training (SET) and underwent muscle biopsy after 3 weeks and 12 weeks of training and had sufficient tissue to measure VEGF-A, VEGF165b and VEGF-R1 concentrations in skeletal muscle lysates by ELISA. Muscle concentrations of VEGF-A and VEGF165b were similar in PAD patients versus controls at baseline. At both time points after the start of SET, VEGF-A levels decreased and there was a trend towards increased VEGF165b concentrations. At baseline, VEGF-R1 concentrations were lower in PAD patients when compared with controls but did not change after SET. Skeletal muscle concentrations of VEGF-A are not different in PAD patients when compared with controls at baseline. SET is associated with a significant reduction in VEGF-A levels and a trend towards increased VEGF165b levels. These somewhat unexpected findings suggest that further investigation into the mechanism of vascular responses to exercise training in PAD patients is warranted.