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Aerobic training and l-arginine supplementation promotes rat heart and hindleg muscles arteriogenesis after myocardial infarction

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Abstract

Arteriogenesis is a main defense mechanism to prevent heart and local tissues dysfunction in occlusive artery disease. TGF-β and angiostatin have a pivotal role in arteriogenesis. We tested the hypothesis that aerobic training and l-arginine supplementation promotes cardiac and skeletal muscles arteriogenesis after myocardial infarction (MI) parallel to upregulation of TGF-β and downregulation of angiostatin. For this purpose, 4 weeks after LAD occlusion, 50 male Wistar rats were randomly distributed into five groups: (1) sham surgery without MI (sham, n = 10), (2) control-MI (Con-MI, n = 10), (3) l-arginine-MI (La-MI, n = 10), (4) exercise training-MI (Ex-MI, n = 10), and (5) exercise and l-arginine-MI (Ex + La-MI). Exercise training groups running on a treadmill for 10 weeks with moderate intensity. Rats in the l-arginine-treated groups drank water containing 4 % l-arginine. Arteriolar density with different diameters (11–25, 26–50, 51–75, and 76–150 μm), TGF-β, and angiostatin gene expression were measured in cardiac (area at risk) and skeletal (soleus and gastrocnemius) muscles. Smaller arterioles decreased in cardiac after MI. Aerobic training and l-arginine increased the number of cardiac arterioles with 11–25 and 26–50 μm diameters parallel to TGF-β overexpression. In gastrocnemius muscle, the number of arterioles/mm2 was only increased in the 11 to 25 μm in response to training with and without l-arginine parallel to angiostatin downregulation. Soleus arteriolar density with different size was not different between experimental groups. Results showed that 10 weeks aerobic exercise training and l-arginine supplementation promotes arteriogenesis of heart and gastrocnemius muscles parallel to overexpression of TGF-β and downregulation of angiostatin in MI rats.

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References

  1. Araki S, Izumiya Y, Hanatani S, Rokutanda T, Usuku H, Akasaki Y, Takeo T, Nakagata N, Walsh K, Ogawa H (2012) Akt1–mediated skeletal muscle growth attenuates cardiac dysfunction and remodeling after experimental myocardial infarction. Circ Heart Fail 5:116–125

    Article  CAS  PubMed  Google Scholar 

  2. Bai R, Liu W, Zhao A, Zhao Z, Jiang D Nitric oxide content and apoptosis rate in steroid-induced avascular necrosis of the femoral head. Exp Ther Med 10:591–597

  3. Bansal A, Dai Q, Chiao YA, Hakala KW, Zhang JQ, Weintraub ST, Lindsey ML (2010) Proteomic analysis reveals late exercise effects on cardiac remodeling following myocardial infarction. J Proteomics 73:2041–2049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Batista M, Rosa J, Lopes R, Lira F, Martins E, Yamashita A, Brum P, Lancha A, Lopes A, Seelaender M (2010) Exercise training changes IL-10/TNF-α ratio in the skeletal muscle of post-MI rats. Cytokine 49:102–108

    Article  CAS  PubMed  Google Scholar 

  5. Bir SC, Pattillo CB, Pardue S, Kolluru GK, Docherty J, Goyette D, Dvorsky P, Kevil CG (2012) Nitrite anion stimulates ischemic arteriogenesis involving NO metabolism. Am J Physiol Heart Circ Physiol 303:178–188

    Article  Google Scholar 

  6. Boroujerdi A, Welser-Alves JV, Tigges U, Milner R (2012) Chronic cerebral hypoxia promotes arteriogenic remodeling events that can be identified by reduced endoglin (CD105) expression and a switch in β1 integrins. J Cereb Blood Flow Metab 32:1820–1830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chantrain CF, Henriet P, Jodele S, Emonard H, Feron O, Courtoy PJ, DeClerck YA, Marbaix E (2006) Mechanisms of pericyte recruitment in tumour angiogenesis: a new role for metalloproteinases. Eur J Cancer 42:310–318

    Article  CAS  PubMed  Google Scholar 

  8. Cherwek DH, Hopkins MB, Thompson MJ, Annex BH, Taylor DA (2000) Fiber type-specific differential expression of angiogenic factors in response to chronic hindlimb ischemia. Am J Physiol Heart Circ Physiol 279:932–938

    Google Scholar 

  9. Cooke JP, Losordo DW (2002) Nitric oxide and angiogenesis. Circulation 105:2133–2135

    Article  PubMed  Google Scholar 

  10. Dedkov EI, Oak K, Christensen LP, Tomanek RJ (2014) Coronary vessels and cardiac myocytes of middle-aged rats demonstrate regional sex-specific adaptation in response to postmyocardial infarction remodeling. Biol Sex Differ 5:1–14

    Article  PubMed  PubMed Central  Google Scholar 

  11. Grundmann S, van Royen N, Pasterkamp G, Gonzalez N, Tijsma EJ, Piek JJ, Hoefer IE (2007) A new Intra-Arterial DeliveryPlatform for Pro-Arteriogenic compounds to stimulate collateral artery growth via transforming growth Factor-β1 release. J Am Coll Cardiol 50:351–358

    Article  CAS  PubMed  Google Scholar 

  12. Hazarika S, Angelo M, Li Y, Aldrich AJ, Odronic SI, Yan Z, Stamler JS, Annex BH (2008) Myocyte specific overexpression of myoglobin impairs angiogenesis after hind-limb ischemia. Arterioscler Thromb Vasc Biol 28:2144–2150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Heuslein JL, Meisner JK, Li X, Song J, Vincentelli H, Leiphart RJ, Ames EG, Blackman BR, Price RJ (2015) Mechanisms of amplified arteriogenesis in collateral artery segments exposed to reversed flow direction. Arterioscler Thromb Vasc Biol 35:2354–2365

    Article  CAS  PubMed  Google Scholar 

  14. Hudlická O, Brown MD, Silgram H (2000) Inhibition of capillary growth in chronically stimulated rat muscles by N G-nitro-l-arginine, nitric oxide synthase inhibitor. Microvasc Res 59:45–51

    Article  PubMed  Google Scholar 

  15. Laughlin MH, Cook JD, Tremble R, Ingram D, Colleran PN, Turk JR (2006) Exercise training produces nonuniform increases in arteriolar density of rat soleus and gastrocnemius muscle. Microcirculation 13:175–186

    Article  PubMed  PubMed Central  Google Scholar 

  16. Leosco D, Rengo G, Iaccarino G, Golino L, Marchese M, Fortunato F, Zincarelli C, Sanzari E, Ciccarelli M, Galasso G (2007) Exercise promotes angiogenesis and improves β-adrenergic receptor signalling in the post-ischaemic failing rat heart. Cardiovasc Res 78:385–94

    Article  PubMed  Google Scholar 

  17. Lloyd PG, Prior BM, Li H, Yang HT, Terjung RL (2005) VEGF receptor antagonism blocks arteriogenesis, but only partially inhibits angiogenesis, in skeletal muscle of exercise-trained rats. Am J Physiol Heart Circ Physiol 288:759–768

    Article  Google Scholar 

  18. Matsunaga T, Weihrauch DW, Moniz MC, Tessmer J, Warltier DC, Chilian WM (2002) Angiostatin inhibits coronary angiogenesis during impaired production of nitric oxide. Circulation 105:2185–2191

    Article  CAS  PubMed  Google Scholar 

  19. Miquerol L, Thireau J, Bideaux P, Sturny R, Richard S, Kelly RG (2015) Endothelial plasticity drives arterial remodeling within the endocardium after myocardial infarction. Circ Res 116:1765–1771

    Article  CAS  PubMed  Google Scholar 

  20. Negishi M, Lu D, Zhang Y-Q, Sawada Y, Sasaki T, Kayo T, Ando J, Izumi T, Kurabayashi M, Kojima I (2001) Upregulatory expression of furin and transforming growth factor-β by fluid shear stress in vascular endothelial cells. Arterioscler Thromb Vasc Biol 21:785–790

    Article  CAS  PubMed  Google Scholar 

  21. Nyberg P, Xie L, Kalluri R (2005) Endogenous inhibitors of angiogenesis. Cancer Res 65:3967–3979

    Article  CAS  PubMed  Google Scholar 

  22. Ogoh S, Hirai T, Nohara R, Taguchi S (2001) Adaptation in properties of skeletal muscle to coronary artery occlusion/reperfusion in rats. Nihon Seirigaku Zasshi 64:225–236

    Google Scholar 

  23. Persson AB, Buschmann E, Lindhorst R, Troidl K, Langhoff R, Schulte K, Buschmann I (2011) Therapeutic arteriogenesis in peripheral arterial disease: combining intervention and passive training. VASA 40:177–187

    Article  Google Scholar 

  24. Price RJ, Owens GK, Skalak TC (1994) Immunohistochemical identification of arteriolar development using markers of smooth muscle differentiation. Evidence that capillary arterialization proceeds from terminal arterioles. Circ Res 75:520–527

    Article  CAS  PubMed  Google Scholar 

  25. Price RJ, Skalak TC (1996) Chronic ∼ 1-adrenergic blockade stimulates terminal and arcade arteriolar development. Am J Physiol 271:752–759

    Google Scholar 

  26. Prior BM, Yang H, Terjung RL (2004) What makes vessels grow with exercise training? J Appl Physiol 97:1119–1128

    Article  PubMed  Google Scholar 

  27. Ranjbar K, Nazem F, Nazari A (2015) Effect of exercise training and l-arginine on oxidative stress and left ventricular function in the post-ischemic failing rat heart. Cardiovasc Toxicol 12:1–8

    Google Scholar 

  28. Ratajczak-Wrona W, Jablonska E, Antonowicz B, Dziemianczyk D, Grabowska SZ (2013) Levels of biological markers of nitric oxide in serum of patients with squamous cell carcinoma of the oral cavity. Int J Oral Sci 5:141–145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Seghers L, Vries MR, Pardali E, Hoefer IE, Hierck BP, Dijke P, Goumans MJ, Quax PH (2012) Shear induced collateral artery growth modulated by endoglin but not by ALK1. J Cell Mol Med 16:2440–2450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Strauch AR (2003) Building better blood vessels: new insight on the molecular control of arteriogenesis. Cardiovasc Res 59:532–533

    Article  CAS  PubMed  Google Scholar 

  31. Suzuki J (2005) Microvascular angioadaptation after endurance training with l‐arginine supplementation in rat heart and hindleg muscles. Exp Physiol 90:763–771

    Article  CAS  PubMed  Google Scholar 

  32. Thomas DP, Hudlicka O, Brown MD, Deveci D (1998) Alterations in small arterioles precede changes in limb skeletal muscle after myocardial infarction. Am J Physiol Heart Circ Physiol 275:1032–1039

    Google Scholar 

  33. Tsai S, Hollenbeck ST, Ryer EJ, Edlin R, Yamanouchi D, Kundi R, Wang C, Liu B, Kent KC (2009) TGF-β through Smad3 signaling stimulates vascular smooth muscle cell proliferation and neointimal formation. Am J Physiol Heart Circ Physiol 297:540–549

    Article  Google Scholar 

  34. van Royen N, Hoefer I, Buschmann I, Heil M, Kostin S, Deindl E, Vogel S, Korff T, Augustin H, Bode C (2002) Exogenous application of transforming growth factor beta 1 stimulates arteriogenesis in the peripheral circulation. FASEB J 16:432–434

    PubMed  Google Scholar 

  35. Vara DS, Punshon G, Sales KM, Hamilton G, Seifalian AM (2006) The effect of shear stress on human endothelial cells seeded on cylindrical viscoelastic conduits: an investigation of gene expression. Biotechnol Appl Biochem 45:119–130

    Article  CAS  PubMed  Google Scholar 

  36. Wajih N, Sane DC (2003) Angiostatin selectively inhibits signaling by hepatocyte growth factor in endothelial and smooth muscle cells. Blood 101:1857–1863

    Article  CAS  PubMed  Google Scholar 

  37. Walter JJ, Sane DC (1999) Angiostatin binds to smooth muscle cells in the coronary artery and inhibits smooth muscle cell proliferation and migration in vitro. Arterioscler Thromb Vasc Biol 19:2041–2048

    Article  CAS  PubMed  Google Scholar 

  38. White FC, Bloor CM, McKirnan MD, Carroll SM (1998) Exercise training in swine promotes growth of arteriolar bed and capillary angiogenesis in heart. J Appl Physiol 85:1160–1168

    CAS  PubMed  Google Scholar 

  39. Xu X, Wan W, Powers AS, Li J, Ji LL, Lao S, Wilson B, Erikson JM, Zhang JQ (2008) Effects of exercise training on cardiac function and myocardial remodeling in post myocardial infarction rats. J Mol Cell Cardiol 44:114–122

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the national elite foundation, Tehran, Iran.

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Correspondence to Farhad Rahmani-Nia.

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Animals used in these experiments were treated in accordance with National Institutes of Health Guide for the Care and Use of Laboratory Animals, and the study protocols were approved by the Institutional Animal Care and Use Committee at Lorestan University of Medical Science.

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The authors declare that they have no conflict of interest.

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Ranjbar, K., Rahmani-Nia, F. & Shahabpour, E. Aerobic training and l-arginine supplementation promotes rat heart and hindleg muscles arteriogenesis after myocardial infarction. J Physiol Biochem 72, 393–404 (2016). https://doi.org/10.1007/s13105-016-0480-x

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  • DOI: https://doi.org/10.1007/s13105-016-0480-x

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