VEGF-A splice variants and related receptor expression in human skeletal muscle following submaximal exercise

• Published in: Journal of applied physiology (1985) 2005-06, Vol.98 (6), p.2137-2146
• Main Authors: Gustafsson, T, Ameln, H, Fischer, H, Sundberg, C. J, Timmons, J. A, Jansson, E
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological - genetics; Adolescent; Adult; Biological and medical sciences; Blood Flow Velocity - genetics; DNA, Recombinant - genetics; Exercise; Exercise Test; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation - genetics; Genetic Variation - genetics; Humans; Male; Medicin och hälsovetenskap; Muscle Contraction - genetics; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Muscular system; Physical Exertion; Receptors, Vascular Endothelial Growth Factor - genetics; Receptors, Vascular Endothelial Growth Factor - metabolism; Reperfusion Injury - physiopathology; Tissues; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.01402.2004

1 Department of Physiology and Pharmacology, and 2 Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska University Hospital, and 3 Center for Genomics and Bioinformatics, Karolinska Institutet, Stockholm, Sweden Submitted 21 December 2004 ; accepted in final form 15 January 2005 VEGF-A contributes to muscle tissue angiogenesis following aerobic exercise training. The temporal response of the VEGF-A isoforms and their target receptors has not been comprehensively profiled in human skeletal muscle. We combined submaximal exercise with and without reduced leg blood flow to establish whether ischemia-induced metabolic stress was an important physiological stimuli responsible for regulating the VEGF-A system in humans. Nine healthy men performed two 45-min bouts of one-leg knee-extension exercise, with and without blood flow restriction. Muscle biopsies were obtained at rest and 2 and 6 h after exercise. Expression (mRNA) of the VEGF-A splice variants and related receptors [VEGF receptor (VEGFR)-1, VEGFR-2, and neuropilin-1] was determined by using qPCR. VEGF-A total expression increased more robustly after exercise with reduced blood flow, and initially this principally reflected an increase in VEGF-A 165 . Six hours after exercise, there was a relatively greater increase in VEGF-A 189 , and this response was not influenced by blood flow conditions. VEGFR-1 mRNA expression increased 2 h after exercise, and neuropilin-1 expression was transiently reduced, while all three receptors increased by 6 h. There was no evidence for the expression of the inhibitory VEGF-A 165B variant in human skeletal muscle. Our study, reflecting both VEGF-A ligand and receptors, implicates metabolic perturbation as a regulator of human muscle angiogenesis and demonstrates that VEGF-A splice variants are distinctly regulated. Our findings also indicate that all three receptor genes exhibit different pretranslational regulation, in response to exercise in humans. vascular endothelial growth factor; angiogenesis; ischemia Address for reprint requests and other correspondence: J. A. Timmons, Karolinska Institute, Berzelius Väg 35, Stockholm 171 77, Sweden (E-mail: Jamie.Timmons{at}cgb.ki.se )