Angiogenic growth factor mRNA responses in muscle to a single bout of exercise
Abstract
A major adaptation to exercise is new capillary formation in skeletal muscle. On the basis of angiogenesis in tumors and during development, several angiogenic growth factors may be involved, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta 1 (TGF-beta 1). In 9-wk-old female Wistar rats, mRNA expression for these three growth factors in gastrocnemius muscle was examined by quantitative Northern analysis after a single 1-h run at 15 or 20 m/min at 10 degrees incline in room air. A third group ran at 15 m/min in 12% O2, and resting control groups were included at inspired O2 fractions of 0.21 and 0.12. Exercise significantly increased mRNA levels two- to fourfold, which was evident over the first 4 h postexercise; by 8 and 24 h, mRNA levels returned to baseline. For all three factors, mRNA levels were significantly higher after exercise at 20 than at 15 m/min. Hypoxia at rest doubled VEGF and TGF-beta 1 message but had no effect on bFGF. Hypoxic exercise further raised VEGF mRNA levels but had no effect on the other factors. We suggest that VEGF, bFGF, and TGF-beta 1 may be involved in the angiogenic response to exercise and that reduced intracellular PO2 (as occurs during normoxic exercise) may be part of the stimulus to such growth factor production.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A single bout of exercise can increase VEGF1 and TGFβ1 expression in muscle, promoting the angiogenic response to exercise.
“This paper demonstrated that a single bout of exercise can increase VEGF1 and TGFβ1 expression in muscle to promote the angiogenic response to exercise.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [198]
Cited by
Sorted by citations
Wang, S., Wang, H., Niemi-Junkola, U., Westby, G. W. M., McHaffie, J. G., Stein, B. E., & Redgrave, P. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20001002)425:4 · Cited by 11 · see citing works
Role of Extracellular Matrix in Adaptation of Tendon and Skeletal Muscle to Mechanical Loading
Kjær, M. (2004) · Physiological Reviews · doi:10.1152/physrev.00031.2003 · Cited by 1,596 · see citing works
Exerkines in health, resilience and disease
Chow, L. S., Gerszten, R. E., Taylor, J. M., Pedersen, B. K., van Praag, H., Trappe, S., Febbraio, M. A., Galis, Z. S., Gao, Y., Haus, J. M., et al. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00641-2 · Cited by 927 · see citing works
Couffinhal, T., Silver, M., Zheng, L., Kearney, M., Witzenbichler, B., & Isner, J. M. (1998) · Europe PMC (PubMed Central) · Cited by 672 · see citing works
What makes vessels grow with exercise training?
Prior, B. M., Yang, H. T., & Terjung, R. L. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00035.2004 · Cited by 511 · see citing works
“The importance of hypoxia as an obvious candidate for the initiation of angiogenesis in active muscle during training was reinforced by data showing that hypoxia enhanced the exercise-induced upregulation of VEGF in rat muscle (10).”
BackgroundMolecular basis of skeletal muscle plasticity-from gene to form and function
Flück, M., & Hoppeler, H. H. (2003) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/s10254-002-0004-7 · Cited by 476 · see citing works
“Data from animal studies further indicate the involvement of other molecules such as angiotensin II, basic fibroblast growth factor and transforming growth factor b1, but not of nitric oxide, in capillary remodelling induced by exercise (Amaral et al. 2001b; Breen et al. 1996; Lloyd et al. 2001; Richardson et al. 1999…”
BackgroundTakano, H., Morita, T., Iida, H., Asada, K., Kato, M., Uno, K., Hirose, K., Matsumoto, A., Takenaka, K., Hirata, Y., et al. (2005) · European Journal of Applied Physiology · doi:10.1007/s00421-005-1389-1 · Cited by 446 · see citing works
“1995), followed by the secretion of VEGF immediately after a single bout of exercise in both animals and humans (Breen et al. 1996; Gustafsson et al. 2002).”
BackgroundWaging war on physical inactivity: using modern molecular ammunition against an ancient enemy.
Booth, F., Chakravarthy, M., Gordon, S., & Spangenburg, E. (2002) · Journal of applied physiology · doi:10.1152/japplphysiol.00073.2002 · Cited by 467 · see citing works
“(28) demonstrated that 1 h of acute, submaximal treadmill running resulted in increases in capillary growth factors, i.”
BackgroundÅberg, N. D., Brywe, K. G., & Isgaard, J. (2006) · The Scientific World JOURNAL · doi:10.1100/tsw.2006.22 · Cited by 387 · see citing works
The Effect of Physical Exercise on Endothelial Function
Francescomarino, S. D., Sciartilli, A., Valerio, V. D., Baldassarre, A. D., & Gallina, S. (2009) · Sports Medicine · doi:10.2165/11317750-000000000-00000 · Cited by 379 · see citing works
Wagner, J. P., Black, I. B., & DiCicco-Bloom, E. M. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-14-06006.1999 · Cited by 373 · see citing works
Gustafsson, T. P., Puntschart, A., Kaijser, L., Jansson, E., & Sundberg, C. J. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.276.2.h679 · Cited by 369 · see citing works
Cardiovascular Adaptations to Exercise Training
Hellsten, Y., & Nyberg, M. (2015) · Comprehensive physiology · doi:10.1002/cphy.c140080 · Cited by 415 · see citing works
Yan, Z., Okutsu, M., Akhtar, Y., & Lira, V. A. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00993.2010 · Cited by 338 · see citing works
Casaburi, R. H., Gosselink, R., Decramer, M., Dekhuijzen, R. P. N., Fournier, M., Lewis, M. I., Maltais, F., Oelberg, D., Reid, M. B., Roca, J., et al. (1999) · American Journal of Respiratory and Critical Care Medicine · Cited by 322 · see citing works
Self-citationHeinemeier, K. M., Olesen, J. L., Haddad, F., Langberg, H., Kjær, M., Baldwin, K. M., & Schjerling, P. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.127639 · Cited by 288 · see citing works
“2005) and to acute endurance exercise and short-term endurance training in rats (Breen et al. 1996; Gavin & Wagner, 2001).”
BackgroundInfluentialJensen, L., Bangsbo, J., & Hellsten, Y. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2003.057711 · Cited by 281 · see citing works
“Furthermore, growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), have been proposed to be of importance for angiogenic processes (Morrow et al. 1990; Breen et al. 1996; Annex et al. 1998).”
BackgroundEgan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278 · see citing works
Geng, T., Li, P., Okutsu, M., Yin, X., Kwek, J., Zhang, M., & Yan, Z. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00481.2009 · Cited by 263 · see citing works
“Angiogenesis, the formation of new capillary from the existing vasculature, is equally important to improved functional capacity after exercise training (11, 22).”
BackgroundInvited review: activity-induced angiogenesis
Egginton, S. (2008) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-008-0563-9 · Cited by 259 · see citing works
“Platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-β (TGFβ) are produced by activated EC and mural cells, and help recruit perivascular cells to growing microvessels, aiding maturation and possibly capillary arterialisation, and play a major role in the regulation of the ECM, respectively.”
InfluentialBreen, E. C. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21579 · Cited by 220 · see citing works
“Furthermore, signals (hypoxia, inflammatory cytokines, reactive oxygen species, nitric oxide, and mechanical stimuli) generated during exercise lead to an increased expression of VEGF [Breen et al., 1996] and exercise training leads to a biphasic increase in VEGF expression with the second peak of expression correlati…”
Self-citationVoluntary running induces fiber type-specific angiogenesis in mouse skeletal muscle
Waters, R. E., Rotevatn, S., Li, P., Annex, B. H., & Yan, Z. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00247.2004 · Cited by 214 · see citing works
“First, various types of muscle contraction, including voluntary running, induce a transient increase in VEGF mRNA (10, 24) and protein in skeletal muscle (2, 7, 13).”
BackgroundAngiogenesis during exercise and training.
Bloor, C. M. (2005) · Angiogenesis · doi:10.1007/s10456-005-9013-x · Cited by 206 · see citing works
“Upregulation of VEGF occurs in rat skeletal muscle following chronic muscle stimulation [27, 42, 43] or with a single bout of moderately intense treadmill running [44].”
BackgroundHaas, T. L., Milkiewicz, M., Davis, S. J., Zhou, A., Egginton, S., Brown, M. D., Madri, J. A., & HUDLICKÁ, O. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.279.4.h1540 · Cited by 207 · see citing works
“by hypoxia or by mechanical stretch (4, 24, 32), has”
BackgroundHuman VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise
Richardson, R. S., Wagner, H. E., Mudaliar, S. R. D., Henry, R. R., Noyszewski, E. A., & Wagner, P. D. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.277.6.h2247 · Cited by 202 · see citing works
Self-citationExercise adaptation attenuates VEGF gene expression in human skeletal muscle
Richardson, R. S., Wagner, H. E., Mudaliar, S. R. D., Saucedo, E., Henry, R. R., & Wagner, P. D. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.279.2.h772 · Cited by 205 · see citing works
Self-citationEffects of exercise on gene expression in human peripheral blood mononuclear cells
Connolly, P. H., Caiozzo, V. J., Zaldivar, F. P., Nemet, D., Larson, J. K., Hung, S., Heck, J. D., Hatfield, G. W., & Cooper, D. M. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00316.2004 · Cited by 198 · see citing works
“VEGF is upregulated in muscle tissue after exercise (9).”
BackgroundCapillary regression in vascular endothelial growth factor-deficient skeletal muscle
Tang, K., Breen, E. C., Gerber, H., Ferrara, N., & Wagner, P. D. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00023.2004 · Cited by 196 · see citing works
Self-citationGrowth regulation of the vascular system: an emerging role for adenosine
Adair, T. H. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00840.2004 · Cited by 193 · see citing works
“VEGF has a major physiological role to induce angiogenesis in exercising muscle (25, 28, 67, 125, 162) and is a survival factor (or maintenance factor) for capillary ECs in resting skeletal muscle (147) as well as in other tissues (53).”
BackgroundGenomics and Genetics in the Biology of Adaptation to Exercise
Bouchard, C., Rankinen, T., & Timmons, J. A. (2011) · Comprehensive physiology · doi:10.1002/cphy.c100059 · Cited by 211 · see citing works
Angiogenic growth factor expression in rat skeletal muscle in response to exercise training
Lloyd, P. G., Prior, B. M., Yang, H. T., & Terjung, R. L. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00743.2002 · Cited by 188 · see citing works
Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan
Özerdem, U., & Stallcup, W. B. (2004) · Angiogenesis · doi:10.1007/s10456-004-4182-6 · Cited by 188 · see citing works
Advances and challenges in skeletal muscle angiogenesis
Olfert, I. M., Baum, O., Hellsten, Y., & Egginton, S. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00635.2015 · Cited by 187 · see citing works
“An acute exercise bout leads to a transient, severalfold increase in expression of VEGF mRNA (16, 48, 108) with levels returning to baseline after 4–6 h of recovery (46, 73).”
Brown, M. D., & HUDLICKÁ, O. (2003) · Angiogenesis · doi:10.1023/a:1025809808697 · Cited by 184 · see citing works
Shimizu, R., Hotta, K., Yamamoto, S., Matsumoto, T., Kamiya, K., Kato, M., Hamazaki, N., Kamekawa, D., Akiyama, A., Kamada, Y., et al. (2016) · European Journal of Applied Physiology · doi:10.1007/s00421-016-3328-8 · Cited by 187 · see citing works
Exercise training in swine promotes growth of arteriolar bed and capillary angiogenesis in heart
White, F. C., Bloor, C. M., McKirnan, M. D., & Carroll, S. M. (1998) · Journal of Applied Physiology · doi:10.1152/jappl.1998.85.3.1160 · Cited by 168 · see citing works
Muscle‐specific VEGF deficiency greatly reduces exercise endurance in mice
Olfert, I. M., Howlett, R. A., Tang, K., Dalton, N. D., Gu, Y., Peterson, K. L., Wagner, P. D., & Breen, E. C. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2008.164384 · Cited by 166 · see citing works
“For instance, numerous studies have implicated VEGF in regulating exercise-induced skeletal muscle angiogenesis in both man and animals (Breen et al. 1996; Gustafsson et al. 1999; Richardson et al. 1999; Olfert et al. 2001; Prior et al. 2003, 2004).”
BackgroundSelf-citationAngiotensin II and VEGF are involved in angiogenesis induced by short-term exercise training
Amaral, S. L., Papanek, P. E., & Greene, A. S. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.281.3.h1163 · Cited by 165 · see citing works
“After the last training period, all animals were anesthetized with pentobarbital sodium within 2 h of exercising (5).”
BackgroundMethodInfluentialSystems Biology of Vascular Endothelial Growth Factors
Gabhann, F. M., & Popel, A. S. (2008) · Microcirculation · doi:10.1080/10739680802095964 · Cited by 162 · see citing works
“Mechanical factors, such as muscle contraction [5,63,103] and exercise [17], and environmental factors, such as hypoxia [132] and inflammation [54], also regulate VEGF expression.”
BackgroundArteriogenesis and angiogenesis in rat ischemic hindlimb: role of nitric oxide
Lloyd, P. G., Yang, H. T., & Terjung, R. L. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.281.6.h2528 · Cited by 163 · see citing works
“Interestingly, both VEGF and bFGF have been found to act via NO (see below), and the mRNA levels of both growth factors are reportedly increased in skeletal muscle by exercise (3, 10).”
BackgroundPro‐ and anti‐angiogenic factors in human skeletal muscle in response to acute exercise and training
Høier, B., Nordsborg, N. B., Andersen, S., Jensen, L., Nybo, L., Bangsbo, J., & Hellsten, Y. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.216135 · Cited by 158 · see citing works
“A limited number of studies in animals and humans have determined levels of angiogenic factors in skeletal muscle at the gene and protein level in association with acute exercise and training (Breen et al. 1996; Lloyd et al. 2003; Rullman et al. 2007), and few studies have addressed how the balance between different p…”
BackgroundAssociation between shear stress, angiogenesis, and VEGF in skeletal muscles in vivo.
Milkiewicz, M., Brown, M. D., Egginton, S., et al. (2001) · PubMed · doi:10.1038/sj/mn/7800074 · Cited by 149 · see citing works
Olfert, I. M., Howlett, R. A., Wagner, P. D., & Breen, E. C. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00347.2010 · Cited by 149 · see citing works
Self-citationBarash, I. A., Mathew, L., Ryan, A. F., Chen, J., & Lieber, R. L. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00211.2003 · Cited by 148 · see citing works
“In addition, three heat shock proteins (HSP70, HSP86, 2 -crystallin) previously implicated in mediating the response of muscle to exercise and stress (26, 80) were upregulated, along with increased expression of TGF- , likely resulting in angiogenesis (15).”
BackgroundGustafsson, T. P. (2001) · Frontiers in bioscience · doi:10.2741/gustafss · Cited by 147 · see citing works
“muscle itself is the source of matrix VEGF (116).”
BackgroundInfluentialRole of TGF-β1 in relation to exercise-induced type I collagen synthesis in human tendinous tissue
Heinemeier, K. M., Langberg, H., Olesen, J. L., & Kjær, M. (2003) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00403.2003 · Cited by 137 · see citing works
“This hypothesis is supported by in vivo studies that show immediate increases in levels of TGF- 1 in rat muscle in response to endurance exercise (4, 16).”
Angiogenic growth factor response to acute systemic exercise in human skeletal muscle
Gavin, T. P., Robinson, C. B., Yeager, R. C., England, J. A., Nifong, L. W., & Hickner, R. C. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00748.2003 · Cited by 136 · see citing works
“In previous reports, the time course of the VEGF mRNA response to exercise was documented in rats (4, 11).”
BackgroundHyldahl, R. D., Nelson, B., Xin, L., Welling, T., Groscost, L., Hubal, M. J., Chipkin, S. R., Clarkson, P. M., & Parcell, A. C. (2015) · The FASEB Journal · doi:10.1096/fj.14-266668 · Cited by 135 · see citing works
“Previous research has established that acute and chronic exercise up-regulate the expression of TGF-b1 mRNA in skeletal muscle (17, 21, 33, 34).”
BackgroundSkeletal Muscle Microvasculature: A Highly Dynamic Lifeline
Latroche, C., Gitiaux, C., Chrétien, F., Desguerre, I., Mounier, R., & Chazaud, B. (2015) · Physiology · doi:10.1152/physiol.00026.2015 · Cited by 134 · see citing works
“One prevailing notion in both human and animal models is that the metabolic needs during exercise lead to an acute and transient local hypoxia (compared with exposure to chronic hypoxia) with the induction of VEGF secretion (14, 129).”
BackgroundAngiogenesis Induced by Electrical Stimulation Is Mediated by Angiotensin II and VEGF
Amaral, S. L., Linderman, J. R., MORSE, M. M., & Greene, A. S. (2001) · Microcirculation · doi:10.1111/j.1549-8719.2001.tb00158.x · Cited by 133 · see citing works
“Many studies have shown that prolonged exposure to a hypoxic environment stimulates VEGF release in vitro (13,16,35) and in vivo (3).”
BackgroundInfluentialAngiogenesis: the role of the microenvironment in flipping the switch
Giordano, F. J., & Johnson, R. S. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00153-2 · Cited by 128 · see citing works
Kivelä, R., Silvennoinen, M., Touvra, A.-M., Lehti, M., Kainulainen, H., & Vihko, V. (2006) · The FASEB Journal · doi:10.1096/fj.05-4780fje · Cited by 129 · see citing works
“This may be due to the time of sample collection (24 h after the last training bout), as the amount of VEGF-A mRNA has been shown to return to baseline values already after 8 h in rat skeletal muscle (17).”
BackgroundExercise-induced VEGF transcriptional activation in brain, lung and skeletal muscle
Tang, K., Xia, F. C., Wagner, P. D., & Breen, E. C. (2009) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2009.10.007 · Cited by 127 · see citing works
“2.2 Treadmill exercise protocol This exercise protocol was modified from a protocol previously used in our laboratory for exercising rats (Breen et al. 1996).”
BackgroundMethodInfluentialSelf-citationExercise Training and Peripheral Arterial Disease
Haas, T. L., Lloyd, P. G., Yang, H., & Terjung, R. L. (2012) · Comprehensive physiology · doi:10.1002/cphy.c110065 · Cited by 141 · see citing works
Gustafsson, T. P., Knutsson, A., Puntschart, A., Kaijser, L., Nordqvist, S., Sundberg, C. J., & Jansson, E. (2002) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-002-0845-6 · Cited by 126 · see citing works
“This is in keeping with earlier findings in the rat [7, 23].”
BackgroundResultInfluentialTang, K., Wagner, P. D., & Breen, E. C. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.21955 · Cited by 125 · see citing works
“L I S S , I N C . functions as a co-factor with ERR to regulate the exercise-induced angiogenic factor, VEGF (Breen et al., 1996; Arany et al., 2008), and PGC-1a knockout mice have recently been reported to exhibit decreases in both skeletal muscle VEGF levels and muscle capillary to fiber ratio…”
BackgroundSelf-citationPGC-1α mediates exercise-induced skeletal muscle VEGF expression in mice
Leick, L., Hellsten, Y., Fentz, J., Lyngby, S. S., Wojtaszewski, J. F. P., Hidalgo, J., & Pilegaard, H. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00076.2009 · Cited by 124 · see citing works
Are the neuroprotective effects of exercise training systemically mediated?
Tari, A. R., Norevik, C. S., Scrimgeour, N. R., Kobro‐Flatmoen, A., Storm‐Mathisen, J., Bergersen, L. H., Wrann, C. D., Selbæk, G., Kivipelto, M., Moreira, J. B. N., et al. (2019) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2019.02.003 · Cited by 120 · see citing works
“In rats, a single bout (1 h) of PA resulted in raised Vegf mRNA levels in skeletal muscle.(128) Similar findings were obtained after chronic muscle stimulation.”
ResultAnnex, B. H., TORGAN, C. E., Lin, P. C., Taylor, D. A., Thompson, M. A., Peters, K. G., & Kraus, W. E. (1998) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1998.274.3.h860 · Cited by 114 · see citing works
Yau, S., Gil‐Mohapel, J., Christie, B. R., & So, K. (2014) · BioMed Research International · doi:10.1155/2014/403120 · Cited by 116 · see citing works
“An animal study has demonstrated that expression of VEGF mRNA reaches the peak levels immediately after exercise training and gradually declines within 2 hours and then returns to basal levels within 8 hr [246].”
BackgroundGLOE, T. R., Sohn, H. Y., Meininger, G. A., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203889200 · Cited by 113 · see citing works
Czarkowska‐Pączek, B., Bartłomiejczyk, I., & Przybylski, J. (2006) · PubMed · Cited by 113 · see citing works
Relationship between capillary angiogenesis, fiber type, and fiber size in chronic systemic hypoxia
Deveci, D., Marshall, J. M., & Egginton, S. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.281.1.h241 · Cited by 113 · see citing works
“Expression of VEGF mRNA and amount of VEGF protein has been shown to increase in skeletal muscle of rats within a few hours of the onset of hypoxia (32) and when exercise is performed during hypoxia (8), although this was not confirmed by Gustafsson et al.”
BackgroundBerton, E., Antonucci, R., & Palange, P. (1999) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.159.supplement_1.15945 · Cited by 111 · see citing works
Prior, B. M., Lloyd, P. G., Ren, J., et al. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00398.2004 · Cited by 109 · see citing works
“On the other hand, for assessment of gene expression, tissue was taken 2 h following the last exercise bout (n 6 per time point per treatment), a time known to permit responses to acute exercise to become manifest (5).”
Höffner, L., Nielsen, J., Langberg, H., & Hellsten, Y. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.037051 · Cited by 108 · see citing works
“It has been shown in studies on laboratory animals that exercise induces an increase in both bFGF and TGF-b mRNA and protein (Morrow et al. 1990; Breen et al. 1996).”
BackgroundLloyd, P. G., Prior, B. M., Li, H., et al. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00786.2004 · Cited by 108 · see citing works
“contractions and immediately after exercise (4, 14, 15).”
BackgroundBey, L., Akunuri, N., Zhao, P., Hoffman, E. P., Hamilton, D. G., & Hamilton, M. T. (2003) · Physiological Genomics · doi:10.1152/physiolgenomics.00001.2002 · Cited by 106 · see citing works
“Vascular endothelial growth factor (VEGF, A) and lipoprotein lipase (LPL, B) mRNA concentrations were measured in total RNA from independent ambulatory control and suspended rats (n 5–6) for the PCR measurements and separately obtained cRNA samples (n 20–29) for microarray analysis.”
ResultInfluentialRecovery from exercise: vulnerable state, window of opportunity, or crystal ball?
Luttrell, M. J., & Halliwill, J. R. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00204 · Cited by 107 · see citing works
Exercise induces interleukin‐8 receptor (CXCR2) expression in human skeletal muscle
Frydelund‐Larsen, L., Penkowa, M., Akerstrom, T., Zankari, A., Nielsen, S., & Pedersen, B. K. (2007) · Experimental Physiology · doi:10.1113/expphysiol.2006.034769 · Cited by 106 · see citing works
“Previous studies have found only a modest effect of exercise on TGF-β expression in skeletal muscle (Smith-McCune & Weidner, 1994; Breen et al. 1996) and neither room air training nor chronic hypoxic training appeared to alter TGF-β mRNA levels significantly (Olfert et al.”
BackgroundOlfert, I. M., Breen, E. C., Mathieu-Costello, O. A., & Wagner, P. D. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.3.1176 · Cited by 106 · see citing works
“The rationale was based on the previous finding that exercise-induced VEGF mRNA levels are dependent on the intensity of exercise and that acute hypoxic exercise enhances VEGF and TGF-b1 mRNA levels (7).”
BackgroundResultInfluentialSelf-citationMilkiewicz, M., HUDLICKÁ, O., Brown, M. D., & Silgram, H. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01105.2004 · Cited by 107 · see citing works
“Work by Wagner and colleagues has described elevated levels of VEGF mRNA in rat muscles after one bout of exercise (9), a response that was eliminated by repeated exercise during training (58).”
BackgroundSkeletal Muscle Capillarity during Hypoxia: VEGF and Its Activation
Breen, E. C., Tang, K., Olfert, M., Knapp, A. E., & Wagner, P. D. (2008) · High Altitude Medicine & Biology · doi:10.1089/ham.2008.1010 · Cited by 103 · see citing works
“In rats exposed to acute (1 h) hypoxia, there is a transient upregulation of VEGF mRNA, which is augmented when rats are simultaneously exercised (Breen et al., 1996).”
Self-citationIncreased expression of VEGF following exercise training in patients with heart failure
Gustafsson, T. P., Bodin, K., Sylvén, C., Gordon, A., Tyni‐Lenné, R., & Jansson, E. (2001) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2001.00816.x · Cited by 99 · see citing works
Association between Shear Stress, Angiogenesis, and VEGF in Skeletal Muscles In Vivo
Milkiewicz, M., Brown, M. D., Egginton, S., & HUDLICKÁ, O. (2001) · Microcirculation · doi:10.1111/j.1549-8719.2001.tb00172.x · Cited by 97 · see citing works
“Hypoxia is well-known to be a potent stimulus for VEGF expression (1) and Breen and colleagues (9) found VEGF upregulated more in skeletal muscles of rats running for 1 hour in hypoxic than normoxic conditions.”
BackgroundInfluentialNitric oxide synthase inhibition attenuates the skeletal muscle VEGF mRNA response to exercise
Gavin, T. P., Spector, D. A., Wagner, H. E., Breen, E. C., & Wagner, P. D. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.4.1192 · Cited by 93 · see citing works
“This speed represents 55% of the speed required to attain maximal oxygen consumption (6).”
BackgroundMethodInfluentialSelf-citationWiik, A., Gustafsson, T. P., Esbjörnsson, M., Johansson, O., Ekman, M., Sundberg, C. J., & Jansson, E. (2005) · Acta Physiologica Scandinavica · doi:10.1111/j.1365-201x.2005.01433.x · Cited by 92 · see citing works
Elevated Basic Fibroblast Growth Factor Levels in Patients With Pulmonary Arterial Hypertension
Benisty, J. I., McLaughlin, V. V., Landzberg, M. J., et al. (2004) · CHEST Journal · doi:10.1378/chest.126.4.1255 · Cited by 92 · see citing works
Anderson, M., Shelke, N. B., Manoukian, O. S., Yu, X., McCullough, L. D., & Kumbar, S. G. (2015) · Critical Reviews in Biomedical Engineering · doi:10.1615/critrevbiomedeng.2015014015 · Cited by 91 · see citing works
Cardiovascular Adaptations to Exercise Training
Hellsten, Y., & Nyberg, M. (2016) · Comprehensive physiology · doi:10.1002/j.2040-4603.2016.tb00672.x · Cited by 92 · see citing works
“Cross sectional data indicate that endurance athletes have higher (205) or similar (80) number of capillaries around Type I versus around Type II fibers and after high intensity training an unaltered distribution of capillaries around Type I and Type II fibers has been observed (210).”
Blood Vessels and the Satellite Cell Niche
Mounier, R., Chrétien, F., & Chazaud, B. (2011) · Current Topics in Developmental Biology · doi:10.1016/b978-0-12-385940-2.00005-x · Cited by 89 · see citing works
“VEGF has been regularly involved in skeletal muscle angiogenesis induced by acute aerobic or resistance exercise in both human and animals (Breen et al., 1996; Gavin et al., 2004; Gustafsson et al., 2007; Hiscock et al., 2003; Prior et al., 2003, 2004).”
BackgroundEffect of Exercise on Cytokines and Growth Mediators in Prepubertal Children
Scheett, T. P., Mills, P. J., Ziegler, M. G., et al. (1999) · Pediatric Research · doi:10.1203/00006450-199910000-00011 · Cited by 89 · see citing works
Gustafsson, T. P., Ameln, H., Fischer, H., Sundberg, C. J., Timmons, J. A., & Jansson, E. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01402.2004 · Cited by 89 · see citing works
“It is worth emphasizing that a variety of detection methods and normalization procedures have produced both positive and neutral data in support of an additive effect of reduced oxygen delivery on contraction-induced increases in VEGF-A mRNA expression (5, 19, 37, 49).”
BackgroundResultFitzpatrick, T. E., & Graham, C. H. (1998) · Experimental Cell Research · doi:10.1006/excr.1998.4240 · Cited by 88 · see citing works
Kivelä, R., Silvennoinen, M., Lehti, M., Jalava, S. E., Vihko, V., & Kainulainen, H. (2008) · Cardiovascular Diabetology · doi:10.1186/1475-2840-7-13 · Cited by 87 · see citing works
“In healthy skeletal muscle several animal and human studies have shown increased VEGF-A expression after acute exercise [16-18] or electrical stimulation [19,20].”
Importance of Anti‐angiogenic Factors in the Regulation of Skeletal Muscle Angiogenesis
Olfert, I. M., & Birot, O. (2011) · Microcirculation · doi:10.1111/j.1549-8719.2011.00092.x · Cited by 84 · see citing works
“Indeed, angio-adaptation is not found to occur after a single bout of exercise, despite clear evidence that one bout of exercise significantly increases many key angiogenic stimulators [5,12,28,39,43,45,81,93,98,99,102].”
BackgroundPhysiological factors influencing capillary growth
Egginton, S. (2010) · Acta Physiologica · doi:10.1111/j.1748-1716.2010.02194.x · Cited by 84 · see citing works
“Whether by short bouts of electrical stimulation (Breen et al. 1996) or exercise (Gustafsson et al. 2002) muscle activity can raise VEGF mRNA expression, while chronic stimulation increases VEGF transcript (Hang et al. 1995) with a concomitant increase in capillarity (Skorjanc et al. 1998),…”
BackgroundSchobersberger, W., Hobisch-Hagen, P., Fries, D., Wiedermann, F., Rieder-Scharinger, J., Villiger, B., Frey, W., Herold, M., Fuchs, D., & Jelkmann, W. (2000) · Immunobiology · doi:10.1016/s0171-2985(00)80078-9 · Cited by 83 · see citing works
Birot, O., Koulmann, N., Peinnequin, A., & Bigard, X. A. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.043026 · Cited by 84 · see citing works
“Consistent with many previous studies (Breen et al. 1996; Asano et al. 1998; Gustafsson et al. 1999; Gavin et al. 2000), the present results show that levels of VEGF mRNA and protein both increased in whole skeletal muscle after a single bout of exercise, by 90 and 72 %, respectively.”
BackgroundMethodResultInfluentialLou, J., Wu, J., Feng, M., Dang, X., Wu, G., Yang, H., Wang, Y., Li, J., Zhao, Y., Shi, C., et al. (2021) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2021.09.009 · Cited by 85 · see citing works
“Even acute exercise bouts increased VEGF mRNA and protein levels transiently in skeletal muscles.(24) 26 Several”
BackgroundEffect of acute exercise and exercise training on VEGF splice variants in human skeletal muscle
Jensen, L., Pilegaard, H., Neufer, P. D., & Hellsten, Y. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00071.2004 · Cited by 81 · see citing works
“Recently studies in human skeletal muscle (10, 14) have revealed that the time course of the total VEGF mRNA response to acute exercise is different from what has been found in rats with VEGF mRNA levels responding faster and returning faster to baseline levels in rats (4).”
BackgroundResultThe critical role of VEGF in skeletal muscle angiogenesis and blood flow
Wagner, P. D. (2011) · Biochemical Society Transactions · doi:10.1042/bst20110646 · Cited by 81 · see citing works
Self-citationZwetsloot, K. A., Westerkamp, L. M., Holmes, B. F., & Gavin, T. P. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.159871 · Cited by 78 · see citing works
“2006) and exercise (Breen et al. 1996; Gustafsson et al. 1999; Gavin et al. 2006); however, the mechanisms that regulate skeletal muscle VEGF expression remain to be elucidated.”
BackgroundEffect of short-term exercise training on angiogenic growth factor gene responses in rats
Gavin, T. P., & Wagner, P. D. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.90.4.1219 · Cited by 79 · see citing works
“(7) demonstrated that bFGF mRNA was increased only immediately after exercise, whereas both VEGF and TGF-b1 were still elevated 2 h after exercise.”
BackgroundMethodInfluentialSelf-citationPhysical Exercise-Induced Myokines in Neurodegenerative Diseases
Lee, B., Shin, M., Park, Y., Won, S.-Y., & Cho, K. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115795 · Cited by 79 · see citing works
Frey, S. P., Jansen, H., Raschke, M. C. E. J., et al. (2012) · Clinical Orthopaedics and Related Research · doi:10.1007/s11999-012-2456-7 · Cited by 77 · see citing works
“Several studies suggest increased VEGF-A expression after acute exercise [5, 11, 14] or electrical stimulation [13, 31].”
BackgroundWagner, P. D. (2001) · Advances in experimental medicine and biology · doi:10.1007/978-1-4757-3401-0_4 · Cited by 73 · see citing works
Self-citationGaudel, C., Schwartz, C., Giordano, C., Abumrad, N. A., & Grimaldi, P. A. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00581.2007 · Cited by 73 · see citing works
Kosmidou, I., Xagorari, A., Roussos, C., & Papapetropoulos, A. (2001) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.2001.280.4.l585 · Cited by 71 · see citing works
“In situ hybridization data (5) revealed the presence of increased mRNA for VEGF in skeletal muscle fibers after exercise, suggesting that myocytes might be the source of this growth factor.”
BackgroundResultBenoit, H. C., Jordan, M. C., Wagner, H. E., et al. (1999) · Journal of Applied Physiology · doi:10.1152/jappl.1999.86.5.1513 · Cited by 71 · see citing works
“We have shown that a single exercise bout (1) and others have found that several days of chronic stimulation (5) in a naı̈ve rat increases VEGF gene expression severalfold as well as that for basic fibroblast growth factor (bFGF) and transforming growth factor-b1 (TGFb1) to a lesser degree, presumably initiating angio…”
BackgroundMethodInfluentialSelf-citation
- Authors
- Breen, E. C., Johnson, E. C., Wagner, H., Tseng, H. M., Sung, L. A., & Wagner, P. D.
- Affiliations
- University of California San Diego (US)
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 1996-07-01
- Volume
- 81
- Issue
- 1
- Pages
- 355-361
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2137609684
- Cited by
- 302
- References
- 0
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 8 · 2020: 7 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 15 · 2015: 21 · 2014: 13 · 2013: 13 · 2012: 13
- FWCI
- 22.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl046910-04)
- National Heart, Lung, and Blood Institute (P01HL017731, 2-PO1-HL-17731, 5-RO1-HL-46910)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- exercise-induced angiogenesis, angiogenic factors, vascular endothelial growth factor, basic fibroblast growth factor, TGF-β1, hypoxic exercise, hypoxia, intracellular oxygen tension, mRNA expression, gastrocnemius, single bout exercise
- MeSH terms
- Animals, Hypoxia, Physical Exertion, Female, Half-Life, RNA, Messenger, Blotting, Northern, Transforming Growth Factor beta, Fibroblast Growth Factor 2, Endothelial Growth Factors, Rats, Wistar, In Situ Hybridization, Muscle, Skeletal, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
