Muscle angiogenic growth factor gene responses to exercise in chronic renal failure
1 Department of Medicine, Section of Physiology, University of California San Diego, La Jolla, California 92093; 2 Muscle Research Unit, 3 Servei de Pneumologia i Allèrgia Respiratòria, and 4 Unitat de Trasplantament Renal, Departament de Medicina, Institut d'Investigacions Biomèdiques Pi i...
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Published in | American journal of physiology. Regulatory, integrative and comparative physiology Vol. 281; no. 2; pp. 539 - R546 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.08.2001
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Subjects | |
Online Access | Get full text |
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Summary: | 1 Department of Medicine, Section of Physiology, University
of California San Diego, La Jolla, California 92093; 2 Muscle
Research Unit, 3 Servei de Pneumologia i Allèrgia
Respiratòria, and 4 Unitat de Trasplantament Renal,
Departament de Medicina, Institut d'Investigacions
Biomèdiques Pi i Sunyer, Hospital Clínic, 08306 Barcelona, Spain
Patients with chronic renal failure (CRF) have
impaired exercise capacity even after erythropoietin treatment. We
recently showed that although this is explained in part by reduced
convective O 2 delivery to muscles, there is also an
impairment of O 2 transport from muscle capillaries to the
mitochondria. Given the importance of the capillary surface area for
capillary mitochondrial O 2 transport and reports of reduced
capillarity in CRF, we hypothesized that the angiogenic gene response
to exercise is impaired in such patients. Six patients with CRF and six
control subjects matched for age, size, and sedentary lifestyle
exercised on a single occasion for 1 h at similar work intensities
averaging 50% of maximal capacity. Exercise was confined to the knee
extensors of a single leg by means of a specially designed leg-kick
ergometer. A percutaneous biopsy of the quadriceps was taken within 30 min of cessation of exercise and compared with a similar biopsy done at
different times without any prior exercise for 24 h. Conventional
Northern blots were prepared and probed for vascular endothelial growth factor (VEGF; the major putative angiogenic growth factor for muscle),
basic fibroblast growth factor (bFGF), and transforming growth factor
(TGF)- 1 . Data during both rest and exercise were successfully obtained in four subjects of each group. We also assessed
muscle capillarity and mitochondrial oxidative capacity to relate to
these changes. Mitochondrial oxidative capacity was normal, whereas
capillary number per fiber was 12% lower than in normal subjects. VEGF
mRNA abundance was increased after exercise by about one order of
magnitude, with no reduction in response in CRF. For bFGF and
TGF- 1 , exercise elicited no response in either group.
Reduced muscle capillarity in CRF does not, therefore, stem from
reduced transcription of VEGF. To the extent that VEGF is important to
exercise-induced angiogenesis in muscle, we suspect a
posttranscriptional aberration in this response occurs in CRF to
explain reduced capillarity.
vasoactive endothelial growth factor; basic fibroblast growth
factor; transforming growth factor- 1 ; skeletal muscle; capillarity; O 2 transport |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0363-6119 1522-1490 |
DOI: | 10.1152/ajpregu.2001.281.2.R539 |