Skeletal myofiber VEGF is essential for the exercise training response in adult mice

被引:63
作者
Delavar, Hamid [1 ]
Nogueira, Leonardo [1 ]
Wagner, Peter D. [1 ]
Hogan, Michael C. [2 ]
Metzger, Daniel [2 ]
Breen, Ellen C. [1 ]
机构
[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[2] Univ Strasbourg, Coll France, IGBMC, INSERM,CNRS, Illkirch Graffenstaden, France
基金
美国国家卫生研究院;
关键词
angiogenesis; exercise; metabolism; peripheral vascular disease; ENDOTHELIAL GROWTH-FACTOR; HINDLIMB ISCHEMIA; SATELLITE CELLS; ENZYME-ACTIVITIES; FIBER TYPE; MUSCLE; ANGIOGENESIS; ENDURANCE; MOUSE; RATS;
D O I
10.1152/ajpregu.00522.2013
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Skeletal myofiber VEGF is essential for the exercise training response in adult mice. Am J Physiol Regul Integr Comp Physiol 306:R586-R595, 2014. First published February 12, 2014; doi:10.1152/ajpregu. 00522.2013.-Vascular endothelial growth factor (VEGF) is exercise responsive, pro-angiogenic, and expressed in several muscle cell types. We hypothesized that in adult mice, VEGF generated within skeletal myofibers (and not other cells within muscle) is necessary for the angiogenic response to exercise training. This was tested in adult conditional, skeletal myofiber-specific VEGF gene-deleted mice (skmVEGF -/-), with VEGF levels reduced by > 80%. After 8 wk of daily treadmill training, speed and endurance were unaltered in skmVEGF -/-mice, but increased by 18% and 99% (P < 0.01), respectively, in controls trained at identical absolute speed, incline, and duration. In vitro, isolated soleus and extensor digitorum longus contractile function was not impaired in skmVEGF -/-mice. However, training-induced angiogenesis was inhibited in plantaris (wild type, 38%, skmVEGF -/-18%, P < 0.01), and gastrocnemius (wild type, 43%, P < 0.01; skmVEGF -/-, 7%, not significant). Capillarity was maintained (different from VEGF gene deletion targeted to multiple cell types) in untrained skmVEGF -/- mice. Arteriogenesis (smooth muscle actin +, artery number, and diameter) and remodeling [vimentin +, 5 '-bromodeoxycytidine (BrdU) +, and F4/80+ cells] occurred in skmVEGF -/-mice, even in the absence of training. skmVEGF -/-mice also displayed a limited oxidative enzyme [citrate synthase and beta-hydroxyacyl CoA dehydrogenase (beta-HAD)] training response; beta-HAD activity levels were elevated in the untrained state. These data suggest that myofiber expressed VEGF is necessary for training responses in capillarity and oxidative capacity and for improved running speed and endurance.
引用
收藏
页码:R586 / R595
页数:10
相关论文
共 49 条
[1]   Regulation of myogenic stem cell behavior by vessel cells The "menage a trois" of satellite cells, periendothelial cells and endothelial cells [J].
Abou-Khalil, Rana ;
Mounier, Remi ;
Chazaud, Benedicte .
CELL CYCLE, 2010, 9 (05) :892-896
[2]   Autocrine and Paracrine Angiopoietin 1/Tie-2 Signaling Promotes Muscle Satellite Cell Self-Renewal [J].
Abou-Khalil, Rana ;
Le Grand, Fabien ;
Pallafacchina, Giorgia ;
Valable, Samuel ;
Authier, Francois-Jerome ;
Rudnicki, Michael A. ;
Gherardi, Romain K. ;
Germain, Stephane ;
Chretien, Fabrice ;
Sotiropoulos, Athanassia ;
Lafuste, Peggy ;
Montarras, Didier ;
Chazaud, Benedicte .
CELL STEM CELL, 2009, 5 (03) :298-309
[3]   Skeletal muscle fatigue: Cellular mechanisms [J].
Allen, D. G. ;
Lamb, G. D. ;
Westerblad, H. .
PHYSIOLOGICAL REVIEWS, 2008, 88 (01) :287-332
[4]   Cytokine profile in quadriceps muscles of patients with severe COPD [J].
Barreiro, E. ;
Schols, A. M. W. J. ;
Polkey, M. I. ;
Galdiz, J. B. ;
Gosker, H. R. ;
Swallow, E. B. ;
Coronell, C. ;
Gea, J. .
THORAX, 2008, 63 (02) :100-107
[5]   Arteriolization of capillaries and FGF-2 upregulation in skeletal muscles of patients with chronic peripheral arterial disease [J].
Baum, O ;
Djonov, V ;
Ganster, M ;
Widmer, M ;
Baumgartner, I .
MICROCIRCULATION, 2005, 12 (06) :527-537
[6]  
Benjamin LE, 1998, DEVELOPMENT, V125, P1591
[7]   Differences in leg muscle activity during running and cycling in humans [J].
Bijker, KE ;
de Groot, G ;
Hollander, AP .
EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY, 2002, 87 (06) :556-561
[8]   High-Mobility Group Box-1 Protein Promotes Angiogenesis After Peripheral Ischemia in Diabetic Mice Through a VEGF-Dependent Mechanism [J].
Biscetti, Federico ;
Straface, Giuseppe ;
De Cristofaro, Raimondo ;
Lancellotti, Stefano ;
Rizzo, Paola ;
Arena, Vincenzo ;
Stigliano, Egidio ;
Pecorini, Giovanni ;
Egashira, Kensuke ;
De Angelis, Giulia ;
Ghirlanda, Giovanni ;
Flex, Andrea .
DIABETES, 2010, 59 (06) :1496-1505
[9]   ENZYME-ACTIVITIES IN SKELETAL-MUSCLES FROM PATIENTS WITH PERIPHERAL ARTERIAL INSUFFICIENCY [J].
BYLUND, AC ;
HAMMARSTEN, J ;
HOLM, J ;
SCHERSTEN, T .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1976, 6 (06) :425-429
[10]   Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2 [J].
Cao, RH ;
Bråkenhielm, E ;
Pawliuk, R ;
Wariaro, D ;
Post, MJ ;
Wahlberg, E ;
Leboulch, P ;
Cao, YH .
NATURE MEDICINE, 2003, 9 (05) :604-613