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Skeletal Muscle Capillarity During Hypoxia: VEGF And Its Activation.

E. Breen, Kechun Tang, M. Olfert, Amy E. Knapp, P. Wagner
Published 2008 · Biology, Medicine

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Long-term exposure of humans and many mammals to hypoxia leads to the activation of several cellular mechanisms within skeletal muscles that compensate for a limited availability of cellular oxygen. One of these cellular mechanisms is to increase the expression of a subset of hypoxia-inducible genes, including the expression of vascular endothelial growth factor (VEGF). The VEGF promoter contains a hypoxic response element (HRE) that can bind the transcription factor, hypoxia-inducible factor-1alpha; (HIF-1alpha), and initiate transcriptional activation of the VEGF gene. VEGF gene expression is critically important for skeletal muscle angiogenesis and VEGF gene deletion in the mouse has been shown to greatly reduce skeletal muscle capillarity. However, HIF-1alpha-dependent transcriptional activation of the VEGF gene may not be the only signaling pathway that leads to increased or maintained VEGF levels under conditions of acute or long-term hypoxia. Additional mechanisms, induced during hypoxic exposure that could signal skeletal muscle VEGF activation include inflammation, possibly linked to reactive O(2) species generation, or a change in cellular energy status as reflected by AMP kinase activity. These pathways may provide quite different mechanisms for VEGF upregulation in the context of muscular activity during long-term exposure to a hypoxic environment such as occurs at high altitude. This review will accordingly discuss the potential cellular signals or stimuli resulting from hypoxic exposure that could increase myocyte VEGF expression. These cellular signals include 1) a decrease in intracellular P(O(2)), 2) skeletal muscle inflammation, associated cytokines and oxidative stress, and 3) an increase in AMP kinase activity and adenosine accompanying a reduction in cellular energy potential.
This paper references
10.2337/db07-0255
Skeletal Muscle Adaptation to Exercise Training
K. Roeckl (2007)
10.1016/J.CMET.2007.01.008
Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis
Richard M. Reznick (2007)
10.1016/S1525-0016(02)00035-7
Adeno-associated viral vector-mediated gene transfer of VEGF normalizes skeletal muscle oxygen tension and induces arteriogenesis in ischemic rat hindlimb.
D. Chang (2003)
10.1152/JAPPLPHYSIOL.00637.2002
Mast cells mediate the microvascular inflammatory response to systemic hypoxia.
D. R. Steiner (2003)
10.1161/01.RES.77.3.638
Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5' enhancer.
Y. Liu (1995)
10.1074/jbc.271.50.32253
Activation of Hypoxia-inducible Transcription Factor Depends Primarily upon Redox-sensitive Stabilization of Its α Subunit*
L. Huang (1996)
10.1212/01.wnl.0000188907.97339.76
Elevated IL-6 and TNF-α levels in patients with ALS: Inflammation or hypoxia?
C. Moreau (2005)
10.1074/jbc.271.5.2746
Post-transcriptional Regulation of Vascular Endothelial Growth Factor by Hypoxia (*)
A. Levy (1996)
10.1152/AJPENDO.00489.2004
Interleukin-1beta and tumor necrosis factor-alpha mediation of endotoxin action on growth hormone.
J. A. Daniel (2005)
10.1074/JBC.271.7.3877
The Mouse Gene for Vascular Endothelial Growth Factor
D. Shima (1996)
10.1007/BF01936933
Human muscle structure after exposure to extreme altitude
H. Hoppeler (2005)
Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells . Possible roles of SP - 1
M. Ryuto (1996)
10.1074/jbc.M209114200
Induction of Hypoxia-inducible Factor-1α by Transcriptional and Translational Mechanisms*
E. Pagé (2002)
10.1152/AJPREGU.1990.259.3.R393
Growth regulation of the vascular system: evidence for a metabolic hypothesis.
T. Adair (1990)
10.1074/JBC.M211999200
Oxidative Stress Regulates Vascular Endothelial Growth Factor-A Gene Transcription through Sp1- and Sp3-dependent Activation of Two Proximal GC-rich Promoter Elements*
G. Schaefer (2003)
10.1023/A:1025809808697
Modulation of physiological angiogenesis in skeletal muscle by mechanical forces: Involvement of VEGF and metalloproteinases
M. Brown (2004)
10.1128/MCB.18.6.3112
Translation of Vascular Endothelial Growth Factor mRNA by Internal Ribosome Entry: Implications for Translation under Hypoxia
I. Stein (1998)
10.1177/153537020322800608
Regulation of Vascular Endothelial Growth Factor Gene Expression in Murine Macrophages by Nitric Oxide and Hypoxia
M. Ramanathan (2003)
10.1111/J.1748-1716.1991.TB09176.X
Operation Everest II: structural adaptations in skeletal muscle in response to extreme simulated altitude.
J. D. Macdougall (1991)
10.1136/pgmj.55.645.475
Birmingham Medical Research Expeditionary Society 1977 Expedition: effect of a Himalayan trek on whole body composition, nitrogen and potassium.
T. Harvey (1979)
10.1055/S-2007-1024846
Morphological adaptations of human skeletal muscle to chronic hypoxia.
H. Hoppeler (1990)
10.1172/JCI30658
Aberrant activation of AMP-activated protein kinase remodels metabolic network in favor of cardiac glycogen storage.
I. Luptak (2007)
10.1113/jphysiol.2006.113357
Vascular endothelial growth factor mRNA and protein do not change in parallel during non‐inflammatory skeletal muscle ischaemia in rat
M. Milkiewicz (2006)
Activation of hypoxiainducible transcription factor depends primarily upon redoxsensitive stabilization of its alpha sub - unit
E. HuangL. (1996)
10.1016/0034-5687(89)90026-1
Skeletal muscle capillary geometry: adaptation to chronic hypoxia.
D. Poole (1989)
10.1152/JAPPLPHYSIOL.00694.2004
Exercise training prevents the inflammatory response to hypoxia in cremaster venules.
Teresa A. Orth (2005)
10.1074/jbc.271.45.28220
Induction of Vascular Endothelial Growth Factor by Tumor Necrosis Factor α in Human Glioma Cells
M. Ryuto (1996)
10.1152/ajpcell.1998.275.3.C766
Interstitial ATP level and degradation in control and postmyocardial infarcted rats.
A. I. Kuz'min (1998)
10.1038/nature03952
A mechanosensory complex that mediates the endothelial cell response to fluid shear stress
E. Tzima (2005)
10.1161/CIRCRESAHA.107.150110
A1 Adenosine Receptor Activation Promotes Angiogenesis and Release of VEGF From Monocytes
A. N. Clark (2007)
10.1006/JMCC.2000.1228
Induction of VEGF gene transcription by IL-1 beta is mediated through stress-activated MAP kinases and Sp1 sites in cardiac myocytes.
T. Tanaka (2000)
10.1152/AJPHEART.2001.281.1.H241
Relationship between capillary angiogenesis, fiber type, and fiber size in chronic systemic hypoxia.
D. Deveci (2001)
10.1152/JAPPL.2001.90.4.1532
Chronic hypoxia attenuates resting and exercise-induced VEGF, flt-1, and flk-1 mRNA levels in skeletal muscle.
I. Olfert (2001)
Nutrition and body composition.
J. Brožek (1965)
Reactive oxygen species stimulate VEGF production from C 2 C 12 skeletal myotubes through a PI 3 K / Akt pathway
I. Kosmidou (2001)
10.1146/ANNUREV.PH.49.030187.002341
Cardiovascular responses to chronic hypoxia.
N. Banchero (1987)
10.1152/JAPPL.2001.91.3.1176
Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia.
I. Olfert (2001)
Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.
G. Semenza (1994)
10.1074/jbc.273.46.30336
Vascular Endothelial Growth Factor Regulates Endothelial Cell Survival through the Phosphatidylinositol 3′-Kinase/Akt Signal Transduction Pathway
H. Gerber (1998)
10.1016/S0002-9440(10)64964-4
Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia.
H. Marti (2000)
O'Brien's
Frank E. Miss Collector Buttolph (1959)
10.1023/B:MCBI.0000009875.30308.7a
Mapping hypoxia-induced bioenergetic rearrangements and metabolic signaling by 18O-assisted 31P NMR and 1H NMR spectroscopy
D. Pucar (2004)
10.1152/JAPPLPHYSIOL.00961.2004
Regression of capillary network in atrophied soleus muscle induced by hindlimb unweighting.
H. Fujino (2005)
10.1038/88842
Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration
B. Oosthuyse (2001)
10.1038/nm0603-669
The biology of VEGF and its receptors
N. Ferrara (2003)
10.1074/JBC.270.22.13333
Transcriptional Regulation of the Rat Vascular Endothelial Growth Factor Gene by Hypoxia (*)
A. Levy (1995)
10.1152/AJPHEART.2000.279.5.H2116
Inhibition of adenosine kinase induces expression of VEGF mRNA and protein in myocardial myoblasts.
J. Gu (2000)
10.1074/JBC.M300643200
AMP-activated Protein Kinase (AMPK) Signaling in Endothelial Cells Is Essential for Angiogenesis in Response to Hypoxic Stress*
D. Nagata (2003)
10.1152/AJPHEART.00133.2005
VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature.
T. Kamba (2006)
10.1074/jbc.271.44.27424
Slowed Release of Thrombin-cleaved Factor VIII from von Willebrand Factor by a Monoclonal and a Human Antibody Is a Novel Mechanism for Factor VIII Inhibition*
E. Saenko (1996)
Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis.
H. Dvorak (1995)
Regulation of the hypoxiainducible transcription factor 1 alpha by the ubiquitinproteasome pathway
J. KallioP. (1999)
10.1152/AJPCELL.00449.2004
Reactive oxygen species formation in the transition to hypoxia in skeletal muscle.
L. Zuo (2005)
10.1016/S0034-5687(98)00006-1
Inflammatory cytokines in BAL fluid and pulmonary hemodynamics in high-altitude pulmonary edema.
K. Kubo (1998)
10.1016/J.ATHEROSCLEROSIS.2004.01.015
HIF-VEGF-VEGFR-2, TNF-alpha and IGF pathways are upregulated in critical human skeletal muscle ischemia as studied with DNA array.
T. T. Tuomisto (2004)
10.1152/AJPHEART.00176.2003
Microvascular oxygen distribution in awake hamster window chamber model during hyperoxia.
A. G. Tsai (2003)
10.1152/AJPREGU.00577.2003
Oxygen-dependent and tissue-specific regulation of erythropoietin gene expression.
J. Fandrey (2004)
10.1113/jphysiol.2006.108944
AMP‐activated protein kinase – development of the energy sensor concept
D. Hardie (2006)
10.1016/0034-5687(85)90057-X
Effects of hypoxia on muscle capillarity in rats.
G. K. Snyder (1985)
10.1113/eph8702377
Chronic Hypoxia Induces Prolonged Angiogenesis in Skeletal Muscles of Rat
D. Deveci (2002)
10.1007/BF00371099
Effects of chronic hypoxia and endurance training on muscle capillarity in rats
A. X. Bigard (2004)
10.1152/PHYSIOLGENOMICS.00023.2004
Capillary regression in vascular endothelial growth factor-deficient skeletal muscle.
Kechun Tang (2004)
10.1074/jbc.M010144200
Regulation of glut1 mRNA by Hypoxia-inducible Factor-1
C. Chen (2001)
10.1074/jbc.274.10.6519
Regulation of the Hypoxia-inducible Transcription Factor 1α by the Ubiquitin-Proteasome Pathway*
P. Kallio (1999)
10.1152/JAPPLPHYSIOL.01298.2006
Hypoxia-induced reactive oxygen species formation in skeletal muscle.
T. Clanton (2007)
10.1074/jbc.271.2.736
Interleukin 6 Induces the Expression of Vascular Endothelial Growth Factor (*)
T. Cohen (1996)
10.1152/JAPPLPHYSIOL.01185.2002
Dissociation between skeletal muscle microvascular PO2 and hypoxia-induced microvascular inflammation.
Sidharth Shah (2003)
Elevated IL-6 and TNF-alpha levels in patients with ALS: inflammation or hypoxia?
C. Moreau (2005)
10.1152/JAPPL.1996.81.1.355
Angiogenic growth factor mRNA responses in muscle to a single bout of exercise.
E. Breen (1996)
10.1006/CYTO.1999.0533
High altitude increases circulating interleukin-6, interleukin-1 receptor antagonist and C-reactive protein.
G. Hartmann (2000)
10.1172/JCI1368
IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses.
Z. Xing (1998)
10.1182/BLOOD.V94.5.1561.417A06_1561_1567
Interleukin-1β and Tumor Necrosis Factor- Stimulate DNA Binding of Hypoxia-Inducible Factor-1
T. Hellwig-Bürgel (1999)
10.1152/ajpheart.1999.277.6.H2247
Human VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise.
R. S. Richardson (1999)
Hypoxia promotes ox
G. L. Wilson (2001)
10.1152/AJPLUNG.2001.280.4.L585
Reactive oxygen species stimulate VEGF production from C(2)C(12) skeletal myotubes through a PI3K/Akt pathway.
I. Kosmidou (2001)
10.1152/JAPPL.1989.66.5.2454
Operation Everest II: adaptations in human skeletal muscle.
H. Green (1989)
10.1152/JAPPL.1988.65.6.2545
Operation Everest. II: Nutrition and body composition.
Madeleine S. Rose (1988)
10.1096/fj.01-0125com
HIF‐1 is expressed in normoxic tissue and displays an organ‐specific regulation under systemic hypoxia
D. M. Stroka (2001)
10.1182/BLOOD-2006-08-040006
Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle.
P. Robach (2007)
10.1152/AJPREGU.00840.2004
Growth regulation of the vascular system: an emerging role for adenosine.
T. Adair (2005)
10.1128/MCB.16.9.4604
Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1.
J. Forsythe (1996)
10.1371/journal.pbio.0020288
Loss of Skeletal Muscle HIF-1α Results in Altered Exercise Endurance
S. Mason (2004)
10.1096/fj.00-0755fje
Hypoxia promotes oxidative base modifications in the pulmonary artery endothelial cell VEGF gene
V. Grishko (2001)
10.1007/s11010-007-9424-7
Periods of systemic partial hypoxia induces apoptosis and inflammation in rat skeletal muscle
N. Aravindan (2007)
10.1161/01.RES.0000163633.10240.3b
AMP-Activated Protein Kinase Signaling Stimulates VEGF Expression and Angiogenesis in Skeletal Muscle
N. Ouchi (2005)
10.1038/380439A0
Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene
N. Ferrara (1996)



This paper is referenced by
Acute regulation of skeletal muscle protein metabolism by nutrients, exercise and hypoxia
Timothy Etheridge (2010)
IHE Y CALIDAD DE VIDA: PROPUESTA DE ACTUACIÓN PARA ESTUDIAR LOS BENEFICIOS EN EL ENVEJECIMIENTO ACTIVO Y SALUDABLE
Miguel Corbí Santamaría (2013)
10.3390/molecules25214905
Anti-Angiogenic Properties of Ginsenoside Rg3
Maryam Nakhjavani (2020)
10.1007/978-4-431-55972-6_6
Regulation of Angiogenesis in the Human Endometrium
Hidetaka Okada (2016)
10.1016/J.JCOT.2019.06.015
Vacuum assisted closure (VAC)/negative pressure wound therapy (NPWT) for difficult wounds: A review.
Pawan Agarwal (2019)
10.1007/s12032-009-9354-1
Clinical significance of vascular endothelial growth factor and connexin43 for predicting pancreatic cancer clinicopathologic parameters
Qi-lian Liang (2010)
10.1080/1745039X.2013.830520
Nano-nutrition of chicken embryos. The effect of silver nanoparticles and ATP on expression of chosen genes involved in myogenesis
F. Sawosz (2013)
10.1152/japplphysiol.00501.2016
Intermittent hypobaric hypoxia combined with aerobic exercise improves muscle morphofunctional recovery after eccentric exercise to exhaustion in trained rats.
D. Rizo-Roca (2017)
10.5041/RMMJ.10022
High-Altitude Illnesses: Physiology, Risk Factors, Prevention, and Treatment
A. Taylor (2011)
10.1093/cvr/cvr203
Silencing of int6 gene restores function of the ischaemic hindlimb in a rat model of peripheral arterial disease.
Noriko Okamoto (2011)
10.1097/PRS.0b013e3181956551
Negative-Pressure Wound Therapy I: The Paradox of Negative-Pressure Wound Therapy
N. Kairinos (2009)
10.1007/s00380-016-0801-6
Repetitive restriction of muscle blood flow enhances mTOR signaling pathways in a rat model
T. Nakajima (2016)
10.1016/j.rmr.2011.04.015
[Diaphragm and skeletal muscle dysfunction in COPD].
M-A Caron (2011)
Effets d’un entraînement en endurance sur les caractéristiques musculaires des patients drépanocytaires homozygotes
A. Merlet (2018)
[Sodium nitrite induces PC12 cell differentiation].
Wenyi Yan (2012)
10.2527/jas.2013-6976
Effect of rate of weight gain of steers during the stocker phase. III. Gene expression of adipose tissues and skeletal muscle in growing-finishing beef cattle.
P. Lancaster (2014)
10.1016/j.tmaid.2016.03.015
Altitude training for elite endurance athletes: A review for the travel medicine practitioner.
G. Flaherty (2016)
10.1096/fj.10.167049
IRF2BP2 is a skeletal and cardiac muscle‐enriched ischemia‐inducible activator of VEGFA expression
Allen C. T. Teng (2010)
10.1530/JME-13-0140
An acetylation rheostat for the control of muscle energy homeostasis.
K. Menzies (2013)
10.1152/ajpregu.00320.2009
Mitochondrial content and distribution changes specific to mouse diaphragm after chronic normobaric hypoxia.
J. Gamboa (2010)
10.15823/SM.2015.31
Influence of skilled athletes’ altitude training on erythropoiesis and angiogenesis processes
Yuliya Vinnichuk (2015)
10.1186/1471-2164-15-834
Population history and genomic signatures for high-altitude adaptation in Tibetan pigs
H. Ai (2014)
The Hypoxic Regulation and Function of Hypoxiainducible Factor 2α (HIF-2α) In an Adrenomedullary Chromaffin Cell Line
S. Brown (2009)
10.1152/ajpcell.00305.2011
Nitric oxide and voluntary exercise together promote quadriceps hypertrophy and increase vascular density in female 18-mo-old mice.
Jeff R S Leiter (2012)
10.1155/2010/137817
Epo Is Relevant Neither for Microvascular Formation Nor for the New Formation and Maintenance of Mice Skeletal Muscle Fibres in Both Normoxia and Hypoxia
Luciana Hagström (2010)
10.1096/fj.10-167049
IRF2BP2 is a skeletal and cardiac muscle-enriched ischemia-inducible activator of VEGFA expression.
Allen C. T. Teng (2010)
10.1111/j.1749-6632.2009.05045.x
Survival in Acute and Severe Low O2 Environment
Priti Azad (2009)
10.3390/nu12071933
Intermittent Hypoxic Exposure with High Dose of Arginine Impact on Circulating Mediators of Tissue Regeneration
A. Zembron-Lacny (2020)
10.1152/japplphysiol.00624.2014
Differential sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy.
C. D. de Theije (2015)
10.4077/CJP.2010.AMK078
Effect of mild intermittent hypoxia on glucose tolerance, muscle morphology and AMPK-PGC-1alpha signaling.
Chung-Yu Chen (2010)
The Origin and Stimuli Implicated in the Expression of Nestin(+) Cardiac Myocyte-like Cells in the Ischemic Heart
John Assimakopoulos (2009)
Microcirculation in skeletal muscle.
O. Hudlická (2011)
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