Capillary growth, ultrastructure remodelling and exercise training in skeletal muscle of essential hypertensive patients

Aim The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can normalize these parameters. Methods To investigate angiogenesis and capillary morphology in essential hypertension, muscle biopsies were ob...

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Published inActa Physiologica Vol. 214; no. 2; pp. 210 - 220
Main Authors Gliemann, L., Buess, R., Nyberg, M., Hoppeler, H., Odriozola, A., Thaning, P., Hellsten, Y., Baum, O., Mortensen, S. P.
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LanguageEnglish
Published England Blackwell Publishing Ltd 01.06.2015
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Abstract Aim The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can normalize these parameters. Methods To investigate angiogenesis and capillary morphology in essential hypertension, muscle biopsies were obtained from m. vastus lateralis in subjects with essential hypertension (n = 10) and normotensive controls (n = 11) before and after 8 weeks of aerobic exercise training. Morphometry was performed after transmission electron microscopy, and protein levels of several angioregulatory factors were determined. Results At baseline, capillary density and capillary‐to‐fibre ratio were not different between the two groups. However, the hypertensive subjects had 9% lower capillary area (12.7 ± 0.4 vs. 13.9 ± 0.2 μm2) and tended to have thicker capillary basement membranes (399 ± 16 vs. 358 ± 13 nm; P = 0.094) than controls. Protein expression of vascular endothelial growth factor (VEGF), VEGF receptor‐2 and thrombospondin‐1 were similar in normotensive and hypertensive subjects, but tissue inhibitor of matrix metalloproteinase was 69% lower in the hypertensive group. After training, angiogenesis was evident by 15% increased capillary‐to‐fibre ratio in the hypertensive subjects only. Capillary area and capillary lumen area were increased by 7 and 15% in the hypertensive patients, whereas capillary basement membrane thickness was decreased by 17% (P < 0.05). VEGF expression after training was increased in both groups, whereas VEGF receptor‐2 was decreased by 25% in the hypertensive patients(P < 0.05). Conclusion Essential hypertension is associated with decreased lumen area and a tendency for increased basement membrane thickening in capillaries of skeletal muscle. Exercise training may improve the diffusion conditions in essential hypertension by altering capillary structure and capillary number.
AbstractList The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can normalize these parameters.AIMThe aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can normalize these parameters.To investigate angiogenesis and capillary morphology in essential hypertension, muscle biopsies were obtained from m. vastus lateralis in subjects with essential hypertension (n = 10) and normotensive controls (n = 11) before and after 8 weeks of aerobic exercise training. Morphometry was performed after transmission electron microscopy, and protein levels of several angioregulatory factors were determined.METHODSTo investigate angiogenesis and capillary morphology in essential hypertension, muscle biopsies were obtained from m. vastus lateralis in subjects with essential hypertension (n = 10) and normotensive controls (n = 11) before and after 8 weeks of aerobic exercise training. Morphometry was performed after transmission electron microscopy, and protein levels of several angioregulatory factors were determined.At baseline, capillary density and capillary-to-fibre ratio were not different between the two groups. However, the hypertensive subjects had 9% lower capillary area (12.7 ± 0.4 vs. 13.9 ± 0.2 μm(2)) and tended to have thicker capillary basement membranes (399 ± 16 vs. 358 ± 13 nm; P = 0.094) than controls. Protein expression of vascular endothelial growth factor (VEGF), VEGF receptor-2 and thrombospondin-1 were similar in normotensive and hypertensive subjects, but tissue inhibitor of matrix metalloproteinase was 69% lower in the hypertensive group. After training, angiogenesis was evident by 15% increased capillary-to-fibre ratio in the hypertensive subjects only. Capillary area and capillary lumen area were increased by 7 and 15% in the hypertensive patients, whereas capillary basement membrane thickness was decreased by 17% (P < 0.05). VEGF expression after training was increased in both groups, whereas VEGF receptor-2 was decreased by 25% in the hypertensive patients(P < 0.05).RESULTSAt baseline, capillary density and capillary-to-fibre ratio were not different between the two groups. However, the hypertensive subjects had 9% lower capillary area (12.7 ± 0.4 vs. 13.9 ± 0.2 μm(2)) and tended to have thicker capillary basement membranes (399 ± 16 vs. 358 ± 13 nm; P = 0.094) than controls. Protein expression of vascular endothelial growth factor (VEGF), VEGF receptor-2 and thrombospondin-1 were similar in normotensive and hypertensive subjects, but tissue inhibitor of matrix metalloproteinase was 69% lower in the hypertensive group. After training, angiogenesis was evident by 15% increased capillary-to-fibre ratio in the hypertensive subjects only. Capillary area and capillary lumen area were increased by 7 and 15% in the hypertensive patients, whereas capillary basement membrane thickness was decreased by 17% (P < 0.05). VEGF expression after training was increased in both groups, whereas VEGF receptor-2 was decreased by 25% in the hypertensive patients(P < 0.05).Essential hypertension is associated with decreased lumen area and a tendency for increased basement membrane thickening in capillaries of skeletal muscle. Exercise training may improve the diffusion conditions in essential hypertension by altering capillary structure and capillary number.CONCLUSIONEssential hypertension is associated with decreased lumen area and a tendency for increased basement membrane thickening in capillaries of skeletal muscle. Exercise training may improve the diffusion conditions in essential hypertension by altering capillary structure and capillary number.
Aim The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can normalize these parameters. Methods To investigate angiogenesis and capillary morphology in essential hypertension, muscle biopsies were obtained from m. vastus lateralis in subjects with essential hypertension (n = 10) and normotensive controls (n = 11) before and after 8 weeks of aerobic exercise training. Morphometry was performed after transmission electron microscopy, and protein levels of several angioregulatory factors were determined. Results At baseline, capillary density and capillary-to-fibre ratio were not different between the two groups. However, the hypertensive subjects had 9% lower capillary area (12.7 plus or minus 0.4 vs. 13.9 plus or minus 0.2 mu m super(2)) and tended to have thicker capillary basement membranes (399 plus or minus 16 vs. 358 plus or minus 13 nm; P = 0.094) than controls. Protein expression of vascular endothelial growth factor (VEGF), VEGF receptor-2 and thrombospondin-1 were similar in normotensive and hypertensive subjects, but tissue inhibitor of matrix metalloproteinase was 69% lower in the hypertensive group. After training, angiogenesis was evident by 15% increased capillary-to-fibre ratio in the hypertensive subjects only. Capillary area and capillary lumen area were increased by 7 and 15% in the hypertensive patients, whereas capillary basement membrane thickness was decreased by 17% (P < 0.05). VEGF expression after training was increased in both groups, whereas VEGF receptor-2 was decreased by 25% in the hypertensive patients(P < 0.05). Conclusion Essential hypertension is associated with decreased lumen area and a tendency for increased basement membrane thickening in capillaries of skeletal muscle. Exercise training may improve the diffusion conditions in essential hypertension by altering capillary structure and capillary number.
Aim The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can normalize these parameters. Methods To investigate angiogenesis and capillary morphology in essential hypertension, muscle biopsies were obtained from m. vastus lateralis in subjects with essential hypertension (n = 10) and normotensive controls (n = 11) before and after 8 weeks of aerobic exercise training. Morphometry was performed after transmission electron microscopy, and protein levels of several angioregulatory factors were determined. Results At baseline, capillary density and capillary‐to‐fibre ratio were not different between the two groups. However, the hypertensive subjects had 9% lower capillary area (12.7 ± 0.4 vs. 13.9 ± 0.2 μm2) and tended to have thicker capillary basement membranes (399 ± 16 vs. 358 ± 13 nm; P = 0.094) than controls. Protein expression of vascular endothelial growth factor (VEGF), VEGF receptor‐2 and thrombospondin‐1 were similar in normotensive and hypertensive subjects, but tissue inhibitor of matrix metalloproteinase was 69% lower in the hypertensive group. After training, angiogenesis was evident by 15% increased capillary‐to‐fibre ratio in the hypertensive subjects only. Capillary area and capillary lumen area were increased by 7 and 15% in the hypertensive patients, whereas capillary basement membrane thickness was decreased by 17% (P < 0.05). VEGF expression after training was increased in both groups, whereas VEGF receptor‐2 was decreased by 25% in the hypertensive patients(P < 0.05). Conclusion Essential hypertension is associated with decreased lumen area and a tendency for increased basement membrane thickening in capillaries of skeletal muscle. Exercise training may improve the diffusion conditions in essential hypertension by altering capillary structure and capillary number.
Aim The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can normalize these parameters. Methods To investigate angiogenesis and capillary morphology in essential hypertension, muscle biopsies were obtained from m. vastus lateralis in subjects with essential hypertension (n = 10) and normotensive controls (n = 11) before and after 8 weeks of aerobic exercise training. Morphometry was performed after transmission electron microscopy, and protein levels of several angioregulatory factors were determined. Results At baseline, capillary density and capillary-to-fibre ratio were not different between the two groups. However, the hypertensive subjects had 9% lower capillary area (12.7 ± 0.4 vs. 13.9 ± 0.2 µm2) and tended to have thicker capillary basement membranes (399 ± 16 vs. 358 ± 13 nm; P = 0.094) than controls. Protein expression of vascular endothelial growth factor (VEGF), VEGF receptor-2 and thrombospondin-1 were similar in normotensive and hypertensive subjects, but tissue inhibitor of matrix metalloproteinase was 69% lower in the hypertensive group. After training, angiogenesis was evident by 15% increased capillary-to-fibre ratio in the hypertensive subjects only. Capillary area and capillary lumen area were increased by 7 and 15% in the hypertensive patients, whereas capillary basement membrane thickness was decreased by 17% (P < 0.05). VEGF expression after training was increased in both groups, whereas VEGF receptor-2 was decreased by 25% in the hypertensive patients(P < 0.05). Conclusion Essential hypertension is associated with decreased lumen area and a tendency for increased basement membrane thickening in capillaries of skeletal muscle. Exercise training may improve the diffusion conditions in essential hypertension by altering capillary structure and capillary number.
The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can normalize these parameters. To investigate angiogenesis and capillary morphology in essential hypertension, muscle biopsies were obtained from m. vastus lateralis in subjects with essential hypertension (n = 10) and normotensive controls (n = 11) before and after 8 weeks of aerobic exercise training. Morphometry was performed after transmission electron microscopy, and protein levels of several angioregulatory factors were determined. At baseline, capillary density and capillary-to-fibre ratio were not different between the two groups. However, the hypertensive subjects had 9% lower capillary area (12.7 ± 0.4 vs. 13.9 ± 0.2 μm(2)) and tended to have thicker capillary basement membranes (399 ± 16 vs. 358 ± 13 nm; P = 0.094) than controls. Protein expression of vascular endothelial growth factor (VEGF), VEGF receptor-2 and thrombospondin-1 were similar in normotensive and hypertensive subjects, but tissue inhibitor of matrix metalloproteinase was 69% lower in the hypertensive group. After training, angiogenesis was evident by 15% increased capillary-to-fibre ratio in the hypertensive subjects only. Capillary area and capillary lumen area were increased by 7 and 15% in the hypertensive patients, whereas capillary basement membrane thickness was decreased by 17% (P < 0.05). VEGF expression after training was increased in both groups, whereas VEGF receptor-2 was decreased by 25% in the hypertensive patients(P < 0.05). Essential hypertension is associated with decreased lumen area and a tendency for increased basement membrane thickening in capillaries of skeletal muscle. Exercise training may improve the diffusion conditions in essential hypertension by altering capillary structure and capillary number.
Author Thaning, P.
Nyberg, M.
Hellsten, Y.
Mortensen, S. P.
Gliemann, L.
Buess, R.
Hoppeler, H.
Odriozola, A.
Baum, O.
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  surname: Gliemann
  fullname: Gliemann, L.
  organization: Integrative Physiology Group, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
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  givenname: R.
  surname: Buess
  fullname: Buess, R.
  organization: Institute of Anatomy, University of Bern, Bern, Switzerland
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  surname: Nyberg
  fullname: Nyberg, M.
  organization: Integrative Physiology Group, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
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  surname: Hoppeler
  fullname: Hoppeler, H.
  organization: Institute of Anatomy, University of Bern, Bern, Switzerland
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  surname: Odriozola
  fullname: Odriozola, A.
  organization: Institute of Anatomy, University of Bern, Bern, Switzerland
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  organization: Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen, Denmark
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  surname: Hellsten
  fullname: Hellsten, Y.
  email: Correspondence: Y. Hellsten, Integrative Physiology Group, Department of Nutrition, Exercise and Sports, University of Copenhagen, Universitetsparken 13, 2100 Copenhagen, Denmark, yhellsten@nexs.ku.dk
  organization: Integrative Physiology Group, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
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  surname: Mortensen
  fullname: Mortensen, S. P.
  organization: Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen, Denmark
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Copyright 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd
2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
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Keywords vascular remodelling
cardiovascular disease
capillaries
high blood pressure
physical activity
Language English
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2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
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Danish Heart Foundation
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Table S1. Baseline characteristics before and after 8 weeks of aerobic exercise training.Data S1. Methodological details for training intervention and Western Blot procedure.
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PublicationCentury 2000
PublicationDate June 2015
PublicationDateYYYYMMDD 2015-06-01
PublicationDate_xml – month: 06
  year: 2015
  text: June 2015
PublicationDecade 2010
PublicationPlace England
PublicationPlace_xml – name: England
– name: Stockholm
PublicationTitle Acta Physiologica
PublicationTitleAlternate Acta Physiol
PublicationYear 2015
Publisher Blackwell Publishing Ltd
Wiley Subscription Services, Inc
Publisher_xml – name: Blackwell Publishing Ltd
– name: Wiley Subscription Services, Inc
References Tang, K., Breen, E.C., Gerber, H.-P., Ferrara, N.M.A. & Wagner, P.D. 2004. Capillary regression in vascular endothelial growth factor-deficient skeletal muscle. Physiol Genomics 18, 63-69.
Baum, O., Ganster, M., Baumgartner, I., Nieselt, K. & Djonov, V. 2007. Basement membrane remodeling in skeletal muscles of patients with limb ischemia involves regulation of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases. J Vasc Res 44, 202-213.
Millauer, B., Wizigmann-Voos, S., Schnürch, H., Martinez, R., Møller, N.P., Risau, W. & Ullrich, A. 1993. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72, 835-846.
Uitto, J., Perejda, A.J., Grant, G.A., Rowold, E.A., Kilo, C. & Williamson, J.R. 1982. Glycosylation of human glomerular basement membrane collagen: increased content of hexose in ketoamine linkage and unaltered hydroxylysine-O-glycosides in patients with diabetes. Connect Tissue Res 10, 287-296.
Plouët, J., Schilling, J. & Gospodarowicz, D. 1989. Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J 8, 3801-3806.
Schiffrin, E.L. 2012. Vascular remodeling in hypertension: mechanisms and treatment. Hypertension 59, 367-374.
Gustafsson, T., Knutsson, A., Puntschart, A., Kaijser, L., Nordqvist, A.S., Sundberg, C.J. & Jansson, E. 2002. Increased expression of vascular endothelial growth factor in human skeletal muscle in response to short-term one-legged exercise training. Pflugers Arch 444, 752-759.
Greene, A.S. & Amaral, S.L. 2002. Microvascular angiogenesis and the renin-angiotensin system. Curr Hypertens Rep 4, 56-62.
Mortensen, S.P., Nyberg, M., Gliemann, L., Thaning, P., Saltin, B. & Hellsten, Y. 2014. Exercise training modulates functional sympatholysis and alpha-adrenergic vasoconstrictor responsiveness in hypertensive and normotensive individuals. J Physiol 592, 3063-3073. doi: 10.1113/jphysiol.2014.273722.
Baum, O., Djonov, V., Ganster, M., Widmer, M. & Baumgartner, I. 2005. Arteriolization of capillaries and FGF-2 upregulation in skeletal muscles of patients with chronic peripheral arterial disease. Microcirculation 12, 527-537.
Ridnour, L.A., Isenberg, J.S., Espey, M.G., Thomas, D.D., Roberts, D.D. & Wink, D.A. 2005. Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1. Proc Natl Acad Sci USA 102, 13147-13152.
Malek, M.H. & Olfert, I.M. 2009. Global deletion of thrombospondin-1 increases cardiac and skeletal muscle capillarity and exercise capacity in mice. Exp Physiol 94, 749-760.
Tan, E.C., Ter Laak, H.J., Hopman, M.T., van Goor, H. & Goris, R.J. 2012. Impaired oxygen utilization in skeletal muscle of CRPS I patients. J Surg Res 173, 145-152.
Melo, R.M., Martinho, E. & Michelini, L.C. 2003. Training-induced, pressure-lowering effect in SHR: wide effects on circulatory profile of exercised and nonexercised muscles. Hypertension 42, 851-857.
Weibel, E.R. 1979. Stereological Methods. Practical Methods for Biological Morphometry. Academic Press, London.
Gliemann, L., Olesen, J., Biensø, R.S., Schmidt, J., Akerstrom, T., Nyberg, M., Lindqvist, A., Bangsbo, J. & Hellsten, Y. 2014. Resveratrol modulates the angiogenic response to exercise training in skeletal muscle of aged men. Am J Physiol Heart Circ Physiol 307, H1111-H1119.
Conway, J. 1984. Hemodynamic aspects of essential hypertension in humans. Physiol Rev 64, 617-660.
Egginton, S. 2009. Invited review: activity-induced angiogenesis. Pflugers Arch 457, 963-977.
Altman, D.G. 1980. Statistics and ethics in medical research: III How large a sample? Br Med J 281, 1336-1338.
Hoppeler, H., Howald, H., Conley, K., Lindstedt, S.L., Claassen, H., Vock, P. & Weibel, E.R. 1985. Endurance training in humans: aerobic capacity and structure of skeletal muscle. J Appl Physiol 59, 320-327.
Andersen, P. & Henriksson, J. 1977. Capillary supply of the quadriceps femoris muscle of man: adaptive response to exercise. J Physiol 270, 677-690.
Hansen, A.H., Nielsen, J.J., Saltin, B. & Hellsten, Y. 2010. Exercise training normalizes skeletal muscle vascular endothelial growth factor levels in patients with essential hypertension. J Hypertens 28, 1176-1185.
Williams, J.L., Weichert, A., Zakrzewicz, A., Da Silva-Azevedo, L., Pries, A.R., Baum, O. & Egginton, S. 2006. Differential gene and protein expression in abluminal sprouting and intraluminal splitting forms of angiogenesis. Clin Sci (Lond) 110, 587-595.
Baum, O., Vieregge, M., Koch, P., Gul, S., Hahn, S., Huber-Abel, F.A.M., Pries, A.R. & Hoppeler, H. 2013. Phenotype of capillaries in skeletal muscle of nNOS-knockout mice. Am J Physiol Regul Integr Comp Physiol 304, R1175-R1182.
Nyberg, M., Gliemann, L., Thaning, P., Hellsten, Y. & Mortensen, S.P. 2012. Role of nitric oxide and prostanoids in the regulation of leg blood flow and blood pressure in humans with essential hypertension: effect of high-intensity aerobic training. J Physiol 590, 1481-1494.
Hernández, N., Torres, S.H., Finol, H.J. & Vera, O. 1999. Capillary changes in skeletal muscle of patients with essential hypertension. Anat Rec 256, 425-432.
Su, W., Gao, F., Lu, J., Wu, W., Zhou, G. & Lu, S. 2012. Levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 mRNAs in patients with primary hypertension or hypertension-induced atherosclerosis. J Int Med Res 40, 986-994.
Cornelissen, V.A. & Fagard, R.H. 2005. Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors. Hypertension 46, 667-675.
Guilbert, J.J. 2003. The world health report 2002 - reducing risks, promoting healthy life. Educ Health (Abingdon) 16, 230.
Olfert, I.M., Breen, E.C., Gavin, T.P. & Wagner, P.D. 2006. Temporal thrombospondin-1 mRNA response in skeletal muscle exposed to acute and chronic exercise. Growth Factors 24, 253-259.
Folkman, J. 1976. The vascularization of tumors. Sci Am 234, 58-73.
Olfert, I.M. & Birot, O. 2011. Importance of anti-angiogenic factors in the regulation of skeletal muscle angiogenesis. Microcirculation 18, 316-330.
Milkiewicz, M., Hudlicka, O., Verhaeg, J., Egginton, S. & Brown, M.D. 2003. Differential expression of Flk-1 and Flt-1 in rat skeletal muscle in response to chronic ischaemia: favourable effect of muscle activity. Clin Sci (Lond) 105, 473-482.
Prior, B.M., Yang, H.T. & Terjung, R.L. 2004. What makes vessels grow with exercise training? J Appl Physiol 97, 1119-1128.
Olfert, I.M., Howlett, R.A., Tang, K., Dalton, N.D., Gu, Y., Peterson, K.L., Wagner, P.D. & Breen, E.C. 2009. Muscle-specific VEGF deficiency greatly reduces exercise endurance in mice. J Physiol 587, 1755-1767.
Hellsten, Y., Jensen, L., Thaning, P., Nyberg, M. & Mortensen, S. 2012b. Impaired formation of vasodilators in peripheral tissue in essential hypertension is normalized by exercise training: role of adenosine and prostacyclin. J Hypertens 30, 2007-2014.
Jones, W.S., Duscha, B.D., Robbins, J.L., Duggan, N.N., Regensteiner, J.G., Kraus, W.E., Hiatt, W.R., Dokun, A.O. & Annex, B.H. 2012. Alteration in angiogenic and anti-angiogenic forms of vascular endothelial growth factor-A in skeletal muscle of patients with intermittent claudication following exercise training. Vasc Med 17, 94-100.
Fagard, R.H. & Cornelissen, V.A. 2007. Effect of exercise on blood pressure control in hypertensive patients. Eur J Cardiovasc Prev Rehabil 14, 12-17.
Gustafsson, T., Puntschart, A., Kaijser, L., Jansson, E. & Sundberg, C.J. 1999. Exercise-induced expression of angiogenesis-related transcription and growth factors in human skeletal muscle. Am J Physiol 276, H679-H685.
Ferrara, N. 2001. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol 280, C1358-C1366.
Olfert, I.M., Howlett, R.A., Wagner, P.D. & Breen, E.C. 2010. Myocyte vascular endothelial growth factor is required for exercise-induced skeletal muscle angiogenesis. Am J Physiol Regul Integr Comp Physiol 299, R1059-R1067.
Perk, J., De Backer, G., Gohlke, H., Graham, I., Reiner, Z., Verschuren, M., Albus, C., Benlian, P., Boysen, G., Cifkova, R. et al. 2012. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J 33, 1635-1701.
Debbabi, H., Uzan, L., Mourad, J.J., Safar, M. & Levy, B.I. 2006. Increased skin capillary density in treated essential hypertensive patients. Am J Hypertens 19, 477-483.
Peterson, C.M., Jones, R.L., Esterly, J.A., Wantz, G.E. & Jackson, R.L. 1980. Changes in basement membrane thickening and pulse volume concomitant with improved glucose control and exercise in patients with insulin-dependent diabetes mellitus. Diabetes Care 3, 586-589.
Tayebjee, M.H., Nadar, S., Blann, A.D., Gareth Beevers, D., MacFadyen, R.J. & Lip, G.Y.H. 2004. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Am J Hypertens 17, 764-769.
Høier, B., Nordsborg, N., Andersen, S., Jensen, L., Nybo, L., Bangsbo, J. & Hellsten, Y. 2012. Pro- and anti-angiogenic factors in human skeletal muscle in response to acute exercise and training. J Physiol 590, 595-606.
Shapiro, S.S. & Wilk, M.B. 1965. An analysis of variance test for normality (complete samples). Biometrika 52, 591-611.
Høier, B., Walker, M., Passos, M., Walker, P.J., Green, A., Bangsbo, J., Askew, C.D. & Hellsten, Y. 2013. Angiogenic response to passive movement and active exercise in individuals with peripheral arterial disease. J Appl Physiol 115, 1777-1787.
Greene, A.S., Tonellato, P.J., Zhang, Z., Lombard, J.H. & Cowley, A.W. 1992. Effect of microvascular rarefaction on tissue oxygen delivery in hypertension. Am J Physiol 262, H1486-H1493.
Henrich, H.A., Romen, W., Heimgärtner, W., Hartung, E. & Bäumer, F. 1988. Capillary rarefaction characteristic of the skeletal muscle of hypertensive patients. Klin Woche
2001; 91
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References_xml – reference: Hansen, A.H., Nielsen, J.J., Saltin, B. & Hellsten, Y. 2010. Exercise training normalizes skeletal muscle vascular endothelial growth factor levels in patients with essential hypertension. J Hypertens 28, 1176-1185.
– reference: Weibel, E.R. 1979. Stereological Methods. Practical Methods for Biological Morphometry. Academic Press, London.
– reference: Guilbert, J.J. 2003. The world health report 2002 - reducing risks, promoting healthy life. Educ Health (Abingdon) 16, 230.
– reference: Fagard, R.H. & Cornelissen, V.A. 2007. Effect of exercise on blood pressure control in hypertensive patients. Eur J Cardiovasc Prev Rehabil 14, 12-17.
– reference: Folkman, J. 1976. The vascularization of tumors. Sci Am 234, 58-73.
– reference: Schiffrin, E.L. 2012. Vascular remodeling in hypertension: mechanisms and treatment. Hypertension 59, 367-374.
– reference: Millauer, B., Wizigmann-Voos, S., Schnürch, H., Martinez, R., Møller, N.P., Risau, W. & Ullrich, A. 1993. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72, 835-846.
– reference: Malek, M.H. & Olfert, I.M. 2009. Global deletion of thrombospondin-1 increases cardiac and skeletal muscle capillarity and exercise capacity in mice. Exp Physiol 94, 749-760.
– reference: Perk, J., De Backer, G., Gohlke, H., Graham, I., Reiner, Z., Verschuren, M., Albus, C., Benlian, P., Boysen, G., Cifkova, R. et al. 2012. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J 33, 1635-1701.
– reference: Uitto, J., Perejda, A.J., Grant, G.A., Rowold, E.A., Kilo, C. & Williamson, J.R. 1982. Glycosylation of human glomerular basement membrane collagen: increased content of hexose in ketoamine linkage and unaltered hydroxylysine-O-glycosides in patients with diabetes. Connect Tissue Res 10, 287-296.
– reference: Egginton, S. 2009. Invited review: activity-induced angiogenesis. Pflugers Arch 457, 963-977.
– reference: Olfert, I.M., Breen, E.C., Gavin, T.P. & Wagner, P.D. 2006. Temporal thrombospondin-1 mRNA response in skeletal muscle exposed to acute and chronic exercise. Growth Factors 24, 253-259.
– reference: Rogers, M.W., Probst, M.M., Gruber, J.J., Berger, R. & Boone, J.B. 1996. Differential effects of exercise training intensity on blood pressure and cardiovascular responses to stress in borderline hypertensive humans. J Hypertens 14, 1369-1375.
– reference: Tayebjee, M.H., Nadar, S., Blann, A.D., Gareth Beevers, D., MacFadyen, R.J. & Lip, G.Y.H. 2004. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Am J Hypertens 17, 764-769.
– reference: Baum, O., Ganster, M., Baumgartner, I., Nieselt, K. & Djonov, V. 2007. Basement membrane remodeling in skeletal muscles of patients with limb ischemia involves regulation of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases. J Vasc Res 44, 202-213.
– reference: Olfert, I.M., Howlett, R.A., Tang, K., Dalton, N.D., Gu, Y., Peterson, K.L., Wagner, P.D. & Breen, E.C. 2009. Muscle-specific VEGF deficiency greatly reduces exercise endurance in mice. J Physiol 587, 1755-1767.
– reference: Gliemann, L., Olesen, J., Biensø, R.S., Schmidt, J., Akerstrom, T., Nyberg, M., Lindqvist, A., Bangsbo, J. & Hellsten, Y. 2014. Resveratrol modulates the angiogenic response to exercise training in skeletal muscle of aged men. Am J Physiol Heart Circ Physiol 307, H1111-H1119.
– reference: Conway, J. 1984. Hemodynamic aspects of essential hypertension in humans. Physiol Rev 64, 617-660.
– reference: Su, W., Gao, F., Lu, J., Wu, W., Zhou, G. & Lu, S. 2012. Levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 mRNAs in patients with primary hypertension or hypertension-induced atherosclerosis. J Int Med Res 40, 986-994.
– reference: Olfert, I.M., Howlett, R.A., Wagner, P.D. & Breen, E.C. 2010. Myocyte vascular endothelial growth factor is required for exercise-induced skeletal muscle angiogenesis. Am J Physiol Regul Integr Comp Physiol 299, R1059-R1067.
– reference: Ridnour, L.A., Isenberg, J.S., Espey, M.G., Thomas, D.D., Roberts, D.D. & Wink, D.A. 2005. Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1. Proc Natl Acad Sci USA 102, 13147-13152.
– reference: Debbabi, H., Uzan, L., Mourad, J.J., Safar, M. & Levy, B.I. 2006. Increased skin capillary density in treated essential hypertensive patients. Am J Hypertens 19, 477-483.
– reference: Tang, K., Breen, E.C., Gerber, H.-P., Ferrara, N.M.A. & Wagner, P.D. 2004. Capillary regression in vascular endothelial growth factor-deficient skeletal muscle. Physiol Genomics 18, 63-69.
– reference: Gustafsson, T., Puntschart, A., Kaijser, L., Jansson, E. & Sundberg, C.J. 1999. Exercise-induced expression of angiogenesis-related transcription and growth factors in human skeletal muscle. Am J Physiol 276, H679-H685.
– reference: Ferrara, N. 2001. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol 280, C1358-C1366.
– reference: Cornelissen, V.A. & Fagard, R.H. 2005. Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors. Hypertension 46, 667-675.
– reference: Andersen, P. & Henriksson, J. 1977. Capillary supply of the quadriceps femoris muscle of man: adaptive response to exercise. J Physiol 270, 677-690.
– reference: Baum, O., Djonov, V., Ganster, M., Widmer, M. & Baumgartner, I. 2005. Arteriolization of capillaries and FGF-2 upregulation in skeletal muscles of patients with chronic peripheral arterial disease. Microcirculation 12, 527-537.
– reference: Prior, B.M., Yang, H.T. & Terjung, R.L. 2004. What makes vessels grow with exercise training? J Appl Physiol 97, 1119-1128.
– reference: Williams, J.L., Weichert, A., Zakrzewicz, A., Da Silva-Azevedo, L., Pries, A.R., Baum, O. & Egginton, S. 2006. Differential gene and protein expression in abluminal sprouting and intraluminal splitting forms of angiogenesis. Clin Sci (Lond) 110, 587-595.
– reference: Greene, A.S., Tonellato, P.J., Zhang, Z., Lombard, J.H. & Cowley, A.W. 1992. Effect of microvascular rarefaction on tissue oxygen delivery in hypertension. Am J Physiol 262, H1486-H1493.
– reference: Tan, E.C., Ter Laak, H.J., Hopman, M.T., van Goor, H. & Goris, R.J. 2012. Impaired oxygen utilization in skeletal muscle of CRPS I patients. J Surg Res 173, 145-152.
– reference: Altman, D.G. 1980. Statistics and ethics in medical research: III How large a sample? Br Med J 281, 1336-1338.
– reference: Baum, O., Vieregge, M., Koch, P., Gul, S., Hahn, S., Huber-Abel, F.A.M., Pries, A.R. & Hoppeler, H. 2013. Phenotype of capillaries in skeletal muscle of nNOS-knockout mice. Am J Physiol Regul Integr Comp Physiol 304, R1175-R1182.
– reference: Jones, W.S., Duscha, B.D., Robbins, J.L., Duggan, N.N., Regensteiner, J.G., Kraus, W.E., Hiatt, W.R., Dokun, A.O. & Annex, B.H. 2012. Alteration in angiogenic and anti-angiogenic forms of vascular endothelial growth factor-A in skeletal muscle of patients with intermittent claudication following exercise training. Vasc Med 17, 94-100.
– reference: Gustafsson, T., Knutsson, A., Puntschart, A., Kaijser, L., Nordqvist, A.S., Sundberg, C.J. & Jansson, E. 2002. Increased expression of vascular endothelial growth factor in human skeletal muscle in response to short-term one-legged exercise training. Pflugers Arch 444, 752-759.
– reference: Henrich, H.A., Romen, W., Heimgärtner, W., Hartung, E. & Bäumer, F. 1988. Capillary rarefaction characteristic of the skeletal muscle of hypertensive patients. Klin Wochenschr 66, 54-60.
– reference: Høier, B., Walker, M., Passos, M., Walker, P.J., Green, A., Bangsbo, J., Askew, C.D. & Hellsten, Y. 2013. Angiogenic response to passive movement and active exercise in individuals with peripheral arterial disease. J Appl Physiol 115, 1777-1787.
– reference: Hoppeler, H., Howald, H., Conley, K., Lindstedt, S.L., Claassen, H., Vock, P. & Weibel, E.R. 1985. Endurance training in humans: aerobic capacity and structure of skeletal muscle. J Appl Physiol 59, 320-327.
– reference: Olfert, I.M. & Birot, O. 2011. Importance of anti-angiogenic factors in the regulation of skeletal muscle angiogenesis. Microcirculation 18, 316-330.
– reference: Greene, A.S. & Amaral, S.L. 2002. Microvascular angiogenesis and the renin-angiotensin system. Curr Hypertens Rep 4, 56-62.
– reference: Mortensen, S.P., Nyberg, M., Gliemann, L., Thaning, P., Saltin, B. & Hellsten, Y. 2014. Exercise training modulates functional sympatholysis and alpha-adrenergic vasoconstrictor responsiveness in hypertensive and normotensive individuals. J Physiol 592, 3063-3073. doi: 10.1113/jphysiol.2014.273722.
– reference: Peterson, C.M., Jones, R.L., Esterly, J.A., Wantz, G.E. & Jackson, R.L. 1980. Changes in basement membrane thickening and pulse volume concomitant with improved glucose control and exercise in patients with insulin-dependent diabetes mellitus. Diabetes Care 3, 586-589.
– reference: Plouët, J., Schilling, J. & Gospodarowicz, D. 1989. Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J 8, 3801-3806.
– reference: Høier, B., Nordsborg, N., Andersen, S., Jensen, L., Nybo, L., Bangsbo, J. & Hellsten, Y. 2012. Pro- and anti-angiogenic factors in human skeletal muscle in response to acute exercise and training. J Physiol 590, 595-606.
– reference: Nyberg, M., Gliemann, L., Thaning, P., Hellsten, Y. & Mortensen, S.P. 2012. Role of nitric oxide and prostanoids in the regulation of leg blood flow and blood pressure in humans with essential hypertension: effect of high-intensity aerobic training. J Physiol 590, 1481-1494.
– reference: Olfert, I.M., Breen, E.C., Mathieu-Costello, O. & Wagner, P.D. 2001. Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia. J Appl Physiol 91, 1176-1184.
– reference: Milkiewicz, M., Hudlicka, O., Verhaeg, J., Egginton, S. & Brown, M.D. 2003. Differential expression of Flk-1 and Flt-1 in rat skeletal muscle in response to chronic ischaemia: favourable effect of muscle activity. Clin Sci (Lond) 105, 473-482.
– reference: Shapiro, S.S. & Wilk, M.B. 1965. An analysis of variance test for normality (complete samples). Biometrika 52, 591-611.
– reference: Hernández, N., Torres, S.H., Finol, H.J. & Vera, O. 1999. Capillary changes in skeletal muscle of patients with essential hypertension. Anat Rec 256, 425-432.
– reference: Hellsten, Y., Jensen, L., Thaning, P., Nyberg, M. & Mortensen, S. 2012b. Impaired formation of vasodilators in peripheral tissue in essential hypertension is normalized by exercise training: role of adenosine and prostacyclin. J Hypertens 30, 2007-2014.
– reference: Melo, R.M., Martinho, E. & Michelini, L.C. 2003. Training-induced, pressure-lowering effect in SHR: wide effects on circulatory profile of exercised and nonexercised muscles. Hypertension 42, 851-857.
– volume: 14
  start-page: 1369
  year: 1996
  end-page: 1375
  article-title: Differential effects of exercise training intensity on blood pressure and cardiovascular responses to stress in borderline hypertensive humans
  publication-title: J Hypertens
– volume: 457
  start-page: 963
  year: 2009
  end-page: 977
  article-title: Invited review: activity‐induced angiogenesis
  publication-title: Pflugers Arch
– volume: 18
  start-page: 316
  year: 2011
  end-page: 330
  article-title: Importance of anti‐angiogenic factors in the regulation of skeletal muscle angiogenesis
  publication-title: Microcirculation
– volume: 17
  start-page: 764
  year: 2004
  end-page: 769
  article-title: Matrix metalloproteinase‐9 and tissue inhibitor of metalloproteinase‐1 in hypertension and their relationship to cardiovascular risk and treatment: a substudy of the Anglo‐Scandinavian Cardiac Outcomes Trial (ASCOT)
  publication-title: Am J Hypertens
– volume: 276
  start-page: H679
  year: 1999
  end-page: H685
  article-title: Exercise‐induced expression of angiogenesis‐related transcription and growth factors in human skeletal muscle
  publication-title: Am J Physiol
– volume: 307
  start-page: H1111
  year: 2014
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Snippet Aim The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training...
The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can...
Aim The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training...
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StartPage 210
SubjectTerms Blood Pressure - physiology
capillaries
Capillaries - ultrastructure
cardiovascular disease
Essential Hypertension
high blood pressure
Humans
Hypertension - metabolism
Muscle, Skeletal - metabolism
Neovascularization, Physiologic - physiology
physical activity
Receptors, Vascular Endothelial Growth Factor - metabolism
Vascular Endothelial Growth Factor A - metabolism
vascular remodelling
Title Capillary growth, ultrastructure remodelling and exercise training in skeletal muscle of essential hypertensive patients
URI https://api.istex.fr/ark:/67375/WNG-0P0VV7L8-Q/fulltext.pdf
https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fapha.12501
https://www.ncbi.nlm.nih.gov/pubmed/25846822
https://www.proquest.com/docview/1680030358
https://www.proquest.com/docview/1680750820
https://www.proquest.com/docview/1694982230
Volume 214
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