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The anti-microbial peptide SR-0379 stimulates human endothelial progenitor cell-mediated repair of peripheral artery diseases

  • Lee, Tae Wook (Department of Physiology, School of Medicine, Pusan National University) ;
  • Heo, Soon Chul (Department of Physiology, School of Medicine, Pusan National University) ;
  • Kwon, Yang Woo (Department of Physiology, School of Medicine, Pusan National University) ;
  • Park, Gyu Tae (Department of Physiology, School of Medicine, Pusan National University) ;
  • Yoon, Jung Won (Department of Physiology, School of Medicine, Pusan National University) ;
  • Kim, Seung-Chul (Department of Obstetrics and Gynecology, School of Medicine, Pusan National University) ;
  • Jang, Il Ho (Department of Oral Biochemistry and Molecular Biology, Pusan National University School of Dentistry) ;
  • Kim, Jae Ho (Department of Physiology, School of Medicine, Pusan National University)
  • Received : 2017.03.10
  • Accepted : 2017.05.23
  • Published : 2017.10.31

Abstract

Ischemia is a serious disease, characterized by an inadequate blood supply to an organ or part of the body. In the present study, we evaluated the effects of the anti-microbial peptide SR-0379 on the stem cell-mediated therapy of ischemic diseases. The migratory and tube-forming abilities of human endothelial progenitor cells (EPCs) were enhanced by treatment with SR-0379 in vitro. Intramuscular administration of SR-0379 into a murine ischemic hindlimb significantly enhanced blood perfusion, decreased tissue necrosis, and increased the number of blood vessels in the ischemic muscle. Moreover, co-administration of SR-0379 with EPCs stimulated blood perfusion in an ischemic hindlimb more than intramuscular injection with either SR-0379 or EPCs alone. This enhanced blood perfusion was accompanied by a significant increase in the number of CD31- and ${\alpha}$-SMA-positive blood vessels in ischemic hindlimb. These results suggest that SR-0379 is a potential drug candidate for potentiating EPC-mediated therapy of ischemic diseases.

Keywords

Angiogenesis;Endothelial progenitor cells;Hindlimb ischemia;Peripheral artery diseases;SR-0379

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

References

  1. Brevetti G, Giugliano G, Brevetti L and Hiatt WR (2010) Inflammation in peripheral artery disease. Circulation 122, 1862-1875 https://doi.org/10.1161/CIRCULATIONAHA.109.918417
  2. Hirsch AT, Treat-Jacobson D, Lando HA and Hatsukami DK (1997) The role of tobacco cessation, antiplatelet and lipid-lowering therapies in the treatment of peripheral arterial disease. Vasc Med 2, 243-251 https://doi.org/10.1177/1358863X9700200314
  3. Jude EB, Oyibo SO, Chalmers N and Boulton AJ (2001) Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome. Diabetes Care 24, 1433-1437 https://doi.org/10.2337/diacare.24.8.1433
  4. Belch JJ, Topol EJ, Agnelli G et al (2003) Critical issues in peripheral arterial disease detection and management: a call to action. Arch Intern Med 163, 884-892 https://doi.org/10.1001/archinte.163.8.884
  5. Youssef F, Gupta P, Mikhailidis DP and Hamilton G (2005) Risk modification in patients with peripheral arterial disease: a retrospective survey. Angiology 56, 279-287 https://doi.org/10.1177/000331970505600307
  6. Annex BH (2013) Therapeutic angiogenesis for critical limb ischaemia. Nat Rev Cardiol 10, 387-396 https://doi.org/10.1038/nrcardio.2013.70
  7. Duan J, Murohara T, Ikeda H et al (2000) Hypercholesterolemia inhibits angiogenesis in response to hindlimb ischemia: nitric oxide-dependent mechanism. Circulation 102, Iii370-376
  8. Duan J, Murohara T, Ikeda H et al (2000) Hyperhomocysteinemia impairs angiogenesis in response to hindlimb ischemia. Arterioscler Thromb Vasc Biol 20, 2579-2585 https://doi.org/10.1161/01.ATV.20.12.2579
  9. Cheng XW, Kuzuya M, Kim W et al (2010) Exercise training stimulates ischemia-induced neovascularization via phosphatidylinositol 3-kinase/Akt-dependent hypoxiainduced factor-1 alpha reactivation in mice of advanced age. Circulation 122, 707-716 https://doi.org/10.1161/CIRCULATIONAHA.109.909218
  10. Djonov V, Baum O and Burri PH (2003) Vascular remodeling by intussusceptive angiogenesis. Cell Tissue Res 314, 107-117 https://doi.org/10.1007/s00441-003-0784-3
  11. Patan S (2004) Vasculogenesis and angiogenesis. Cancer Treat Res 117, 3-32
  12. Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH and Verfaillie CM (2002) Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest 109, 337-346 https://doi.org/10.1172/JCI0214327
  13. Hristov M and Weber C (2004) Endothelial progenitor cells: characterization, pathophysiology, and possible clinical relevance. J Cell Mol Med 8, 498-508 https://doi.org/10.1111/j.1582-4934.2004.tb00474.x
  14. Urbich C and Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95, 343-353 https://doi.org/10.1161/01.RES.0000137877.89448.78
  15. Rouhl RP, van Oostenbrugge RJ, Damoiseaux J, Tervaert JW and Lodder J (2008) Endothelial progenitor cell research in stroke: a potential shift in pathophysiological and therapeutical concepts. Stroke 39, 2158-2165 https://doi.org/10.1161/STROKEAHA.107.507251
  16. Zampetaki A, Kirton JP and Xu Q (2008) Vascular repair by endothelial progenitor cells. Cardiovasc Res 78, 413-421 https://doi.org/10.1093/cvr/cvn081
  17. Krenning G, van Luyn MJ and Harmsen MC (2009) Endothelial progenitor cell-based neovascularization: implications for therapy. Trends Mol Med 15, 180-189 https://doi.org/10.1016/j.molmed.2009.02.001
  18. Asahara T, Takahashi T, Masuda H et al (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. Embo j 18, 3964-3972 https://doi.org/10.1093/emboj/18.14.3964
  19. Xu S, Zhu J, Yu L and Fu G (2012) Endothelial progenitor cells: current development of their paracrine factors in cardiovascular therapy. J Cardiovasc Pharmacol 59, 387-396 https://doi.org/10.1097/FJC.0b013e3182440338
  20. Tomioka H, Nakagami H, Tenma A et al (2014) Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway. PLoS One 9, e92597 https://doi.org/10.1371/journal.pone.0092597
  21. Nishikawa T, Nakagami H, Maeda A et al (2009) Development of a novel antimicrobial peptide, AG-30, with angiogenic properties. J Cell Mol Med 13, 535-546 https://doi.org/10.1111/j.1582-4934.2008.00341.x
  22. Nakagami H, Nishikawa T, Tamura N et al (2012) Modification of a novel angiogenic peptide, AG30, for the development of novel therapeutic agents. J Cell Mol Med 16, 1629-1639 https://doi.org/10.1111/j.1582-4934.2011.01406.x
  23. Smith LE, Shen W, Perruzzi C et al (1999) Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Nat Med 5, 1390-1395 https://doi.org/10.1038/70963
  24. Rabinovsky ED and Draghia-Akli R (2004) Insulin-like growth factor I plasmid therapy promotes in vivo angiogenesis. Mol Ther 9, 46-55
  25. Fan W, Sun D, Liu J et al (2012) Adipose stromal cells amplify angiogenic signaling via the VEGF/mTOR/Akt pathway in a murine hindlimb ischemia model: a 3D multimodality imaging study. PLoS One 7, e45621 https://doi.org/10.1371/journal.pone.0045621
  26. Woo KY, Coutts PM and Sibbald RG (2012) A randomized controlled trial to evaluate an antimicrobial dressing with silver alginate powder for the management of chronic wounds exhibiting signs of critical colonization. Adv Skin Wound Care 25, 503-508 https://doi.org/10.1097/01.ASW.0000422628.63148.4b

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