Document Detail

VEGF-A splice variants and related receptor expression in human skeletal muscle following submaximal exercise.
MedLine Citation:
PMID:  15661835     Owner:  NLM     Status:  MEDLINE    
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.
T Gustafsson; H Ameln; H Fischer; C J Sundberg; J A Timmons; E Jansson
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2005-01-20
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  98     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-16     Completed Date:  2005-08-19     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2137-46     Citation Subset:  IM    
Karolinska Institute, Berzelius Väg 35, Stockholm 171 77, Sweden.
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MeSH Terms
Adaptation, Physiological / genetics
Blood Flow Velocity / genetics
DNA, Recombinant / genetics
Exercise Test
Gene Expression Regulation / genetics
Genetic Variation / genetics
Muscle Contraction / genetics
Muscle, Skeletal / blood supply,  metabolism*
Physical Exertion*
Receptors, Vascular Endothelial Growth Factor / genetics*,  metabolism*
Reperfusion Injury / physiopathology*
Vascular Endothelial Growth Factor A / genetics*,  metabolism*
Reg. No./Substance:
0/DNA, Recombinant; 0/Vascular Endothelial Growth Factor A; EC, Vascular Endothelial Growth Factor

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