Angiogenic Response to Passive Movement and Active Exercise in Individuals with Peripheral Arterial Disease

Overview

Journal J Appl Physiol (1985)

Publisher American Physiological Society

Date 2013 Oct 26

PMID 24157526

Citations 31

Authors

B Hoier

M Walker

M Passos

P J Walker

A Green

J Bangsbo

C D Askew

Y Hellsten

Affiliations

Soon will be listed here.

Abstract

Peripheral arterial disease (PAD) is caused by atherosclerosis and is associated with microcirculatory impairments in skeletal muscle. The present study evaluated the angiogenic response to exercise and passive movement in skeletal muscle of PAD patients compared with healthy control subjects. Twenty-one PAD patients and 17 aged control subjects were randomly assigned to either a passive movement or an active exercise study. Interstitial fluid microdialysate and tissue samples were obtained from the thigh skeletal muscle. Muscle dialysate vascular endothelial growth factor (VEGF) levels were modestly increased in response to either passive movement or active exercise in both subject groups. The basal muscle dialysate level of the angiostatic factor thrombospondin-1 protein was markedly higher (P < 0.05) in PAD patients compared with the control subjects, whereas soluble VEGF receptor-1 dialysate levels were similar in the two groups. The basal VEGF protein content in the muscle tissue samples was ∼27% lower (P < 0.05) in the PAD patients compared with the control subjects. Analysis of mRNA expression for a range of angiogenic and angiostatic factors revealed a modest change with active exercise and passive movement in both groups, except for an increase (P < 0.05) in the ratio of angiopoietin-2 to angiopoietin-1 mRNA in the PAD group with both interventions. PAD patients and aged individuals showed a similar limited angiogenic response to active exercise and passive movement. The limited increase in muscle extracellular VEGF combined with an elevated basal level of thrombospondin-1 in muscle extracellular fluid of PAD patients may restrict capillary growth in these patients.

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References

Hoier B, Olsen K, Nyberg M, Bangsbo J, Hellsten Y . Contraction-induced secretion of VEGF from skeletal muscle cells is mediated by adenosine. Am J Physiol Heart Circ Physiol. 2010; 299(3):H857-62. DOI: 10.1152/ajpheart.00082.2010. View

Rullman E, Rundqvist H, Wagsater D, Fischer H, Eriksson P, Sundberg C . A single bout of exercise activates matrix metalloproteinase in human skeletal muscle. J Appl Physiol (1985). 2007; 102(6):2346-51. DOI: 10.1152/japplphysiol.00822.2006. View

Maisonpierre P, Suri C, Jones P, Bartunkova S, Wiegand S, Radziejewski C . Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997; 277(5322):55-60. DOI: 10.1126/science.277.5322.55. View

Gustafsson T, Puntschart A, Kaijser L, Jansson E, Sundberg C . Exercise-induced expression of angiogenesis-related transcription and growth factors in human skeletal muscle. Am J Physiol. 1999; 276(2):H679-85. DOI: 10.1152/ajpheart.1999.276.2.H679. View

Hammarsten J, Holm J, Schersten T, Krotkiewski M . Capillary supply and muscle fibre types in patients with intermittent claudication: relationships between morphology and metabolism. Eur J Clin Invest. 1980; 10(4):301-5. DOI: 10.1111/j.1365-2362.1980.tb00037.x. View

Bongrazio M, Da Silva-Azevedo L, Bergmann E, Baum O, Hinz B, Pries A . Shear stress modulates the expression of thrombospondin-1 and CD36 in endothelial cells in vitro and during shear stress-induced angiogenesis in vivo. Int J Immunopathol Pharmacol. 2006; 19(1):35-48. View

Hellsten Y, Nielsen J, Lykkesfeldt J, Bruhn M, Silveira L, Pilegaard H . Antioxidant supplementation enhances the exercise-induced increase in mitochondrial uncoupling protein 3 and endothelial nitric oxide synthase mRNA content in human skeletal muscle. Free Radic Biol Med. 2007; 43(3):353-61. DOI: 10.1016/j.freeradbiomed.2007.02.029. View

Egginton S . Invited review: activity-induced angiogenesis. Pflugers Arch. 2008; 457(5):963-77. DOI: 10.1007/s00424-008-0563-9. View

Malek M, Olfert I . Global deletion of thrombospondin-1 increases cardiac and skeletal muscle capillarity and exercise capacity in mice. Exp Physiol. 2009; 94(6):749-60. DOI: 10.1113/expphysiol.2008.045989. View

10.

Nyberg M, Blackwell J, Damsgaard R, Jones A, Hellsten Y, Mortensen S . Lifelong physical activity prevents an age-related reduction in arterial and skeletal muscle nitric oxide bioavailability in humans. J Physiol. 2012; 590(21):5361-70. PMC: 3515824. DOI: 10.1113/jphysiol.2012.239053. View

11.

Richardson R, Wagner H, Mudaliar S, Henry R, Noyszewski E, Wagner P . Human VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise. Am J Physiol. 1999; 277(6):H2247-52. DOI: 10.1152/ajpheart.1999.277.6.H2247. View

12.

Makitie J . Skeletal muscle capillaries in intermittent claudication. Arch Pathol Lab Med. 1977; 101(9):500-3. View

13.

Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z . Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999; 13(1):9-22. View

14.

Rissanen T, Vajanto I, Hiltunen M, Rutanen J, Kettunen M, Niemi M . Expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 (KDR/Flk-1) in ischemic skeletal muscle and its regeneration. Am J Pathol. 2002; 160(4):1393-403. PMC: 1867222. DOI: 10.1016/S0002-9440(10)62566-7. View

15.

Choksy S, Pockley A, Wajeh Y, Chan P . VEGF and VEGF receptor expression in human chronic critical limb ischaemia. Eur J Vasc Endovasc Surg. 2004; 28(6):660-9. DOI: 10.1016/j.ejvs.2004.09.001. View

16.

Nordsborg N, Mohr M, Pedersen L, Nielsen J, Langberg H, Bangsbo J . Muscle interstitial potassium kinetics during intense exhaustive exercise: effect of previous arm exercise. Am J Physiol Regul Integr Comp Physiol. 2003; 285(1):R143-8. DOI: 10.1152/ajpregu.00029.2003. View

17.

Breen E, Johnson E, Wagner H, Tseng H, SUNG L, Wagner P . Angiogenic growth factor mRNA responses in muscle to a single bout of exercise. J Appl Physiol (1985). 1996; 81(1):355-61. DOI: 10.1152/jappl.1996.81.1.355. View

18.

Mortensen S, Askew C, Walker M, Nyberg M, Hellsten Y . The hyperaemic response to passive leg movement is dependent on nitric oxide: a new tool to evaluate endothelial nitric oxide function. J Physiol. 2012; 590(17):4391-400. PMC: 3473293. DOI: 10.1113/jphysiol.2012.235952. View

19.

Gustafsson T, Ameln H, Fischer H, Sundberg C, Timmons J, Jansson E . VEGF-A splice variants and related receptor expression in human skeletal muscle following submaximal exercise. J Appl Physiol (1985). 2005; 98(6):2137-46. DOI: 10.1152/japplphysiol.01402.2004. View

20.

Palmer-Kazen U, Religa P, Wahlberg E . Exercise in patients with intermittent claudication elicits signs of inflammation and angiogenesis. Eur J Vasc Endovasc Surg. 2009; 38(6):689-96. DOI: 10.1016/j.ejvs.2009.08.005. View