DOI QR코드

DOI QR Code

Angiopoietin-Like 4 Is Involved in the Poor Angiogenic Potential of High Glucose-Insulted Bone Marrow Stem Cells

  • Kim, Yong Sook (Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital) ;
  • Kang, Hea Jin (Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital) ;
  • Hong, Moon Hwa (Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital) ;
  • Kang, Wan Seok (Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital) ;
  • Choe, Nakwon (Department of Pharmacology and Medical Research Center for Gene Regulation, Chonnam National University Medical School) ;
  • Kook, Hyun (Department of Pharmacology and Medical Research Center for Gene Regulation, Chonnam National University Medical School) ;
  • Jeong, Myung Ho (Cardiovascular Convergence Research Center, Chonnam National University Hospital) ;
  • Ahn, Youngkeun (Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital)
  • 투고 : 2014.01.16
  • 심사 : 2014.03.13
  • 발행 : 2014.03.30

초록

Background and Objectives: Diabetes is reported to reduce the function or number of progenitor cells. We compared the gene expression patterns of bone marrow-derived mesenchymal stem cells from diabetic (DM-BMCs) and healthy (non-DM-BMCs) rats and suggested Angiopoietin-like 4 (Angptl4) could be a responsible factor for impaired angiogenesis of DM-BMCs. Subjects and Methods: BMCs were isolated from DM or non-DM rat, and in vitro angiogenesis activity was compared by tube formation assay on Matrigel and complementary deoxyribonucleic acid expression was analyzed by microarray with or without oxytocin treatment. Human BMCs (hBMCs) were treated with high glucose, and were performed polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. Angptl4 plasmid DNA and micro ribonucleic acid-132 (miR-132) were transfected to immortalized hBMCs. Results: In vitro angiogenesis assay showed the impaired tube formation in DM-BMCs, and slightly recovery by oxytocin treatment. Angptl4, an adipokine, was upregulated in DM-BMCs compared to non-DM-BMCs. Oxytocin treatment reduced Angptl4 in DM-BMCs. In hBMCs, overexpression of Angptl4 attenuated the tube formation. In addition to Angptl4, miR-132 was increased by high glucose treatment. Collectively, high glucose resulted in impaired tube formation through miR-132 induction and Angptl4 upregulation in BMCs. Conclusion: Our results show that the angiogenic activity of BMCs is impaired by high glucose stress, which would be mediated by Angptl4 and miR-132.

키워드

과제정보

연구 과제 주관 기관 : Korean Society of Cardiology

참고문헌

  1. Miyahara Y, Nagaya N, Kataoka M, et al. Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 2006;12:459-65. https://doi.org/10.1038/nm1391
  2. Kim YS, Kwon JS, Hong MH, et al. Restoration of angiogenic capacity of diabetes-insulted mesenchymal stem cells by oxytocin. BMC Cell Biol 2013;14:38. https://doi.org/10.1186/1471-2121-14-38
  3. Fadini GP, Sartore S, Schiavon M, et al. Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia-reperfusion injury in rats. Diabetologia 2006;49:3075-84. https://doi.org/10.1007/s00125-006-0401-6
  4. Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003;348: 593-600. https://doi.org/10.1056/NEJMoa022287
  5. Porrello ER, Olson EN. Building a new heart from old parts: stem cell turnover in the aging heart. Circ Res 2010;107:1292-4. https://doi.org/10.1161/CIRCRESAHA.110.235168
  6. Grundy SM, Benjamin IJ, Burke GL, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 1999;100:1134-46. https://doi.org/10.1161/01.CIR.100.10.1134
  7. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics-- 2011 update: a report from the American Heart Association. Circulation 2011;123:e18-209. https://doi.org/10.1161/CIR.0b013e3182009701
  8. Orchard TJ, Costacou T, Kretowski A, Nesto RW. Type 1 diabetes and coronary artery disease. Diabetes Care 2006;29:2528-38. https://doi.org/10.2337/dc06-1161
  9. Cull CA, Jensen CC, Retnakaran R, Holman RR. Impact of the metabolic syndrome on macrovascular and microvascular outcomes in type 2 diabetes mellitus: United Kingdom Prospective Diabetes Study 78. Circulation 2007;116:2119-26. https://doi.org/10.1161/CIRCULATIONAHA.107.733428
  10. Rivard A, Silver M, Chen D, et al. Rescue of diabetes-related impairment of angiogenesis by intramuscular gene therapy with adeno- VEGF. Am J Pathol 1999;154:355-63. https://doi.org/10.1016/S0002-9440(10)65282-0
  11. Loomans CJ, de Koning EJ, Staal FJ, et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes 2004;53:195-9. https://doi.org/10.2337/diabetes.53.1.195
  12. Dernbach E, Randriamboavonjy V, Fleming I, Zeiher AM, Dimmeler S, Urbich C. Impaired interaction of platelets with endothelial progenitor cells in patients with cardiovascular risk factors. Basic Res Cardiol 2008; 103:572-81. https://doi.org/10.1007/s00395-008-0734-z
  13. Yang YH, Wang Y, Lam KS, et al. Suppression of the Raf/MEK/ERK signaling cascade and inhibition of angiogenesis by the carboxyl terminus of angiopoietin-like protein 4. Arterioscler Thromb Vasc Biol 2008;28: 835-40. https://doi.org/10.1161/ATVBAHA.107.157776
  14. Ito Y, Oike Y, Yasunaga K, et al. Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4. Cancer Res 2003;63: 6651-7.
  15. Ma T, Jham BC, Hu J, et al. Viral G protein-coupled receptor up-regulates Angiopoietin-like 4 promoting angiogenesis and vascular permeability in Kaposi's sarcoma. Proc Natl Acad Sci U S A 2010;107:14363-8. https://doi.org/10.1073/pnas.1001065107
  16. Okochi-Takada E, Hattori N, Tsukamoto T, et al. ANGPTL4 is a secreted tumor suppressor that inhibits angiogenesis. Oncogene 2013. [Epub ahead of print]
  17. Anand S, Majeti BK, Acevedo LM, et al. MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nat Med 2010;16:909-14. https://doi.org/10.1038/nm.2186
  18. Westenskow PD, Kurihara T, Aguilar E, et al. Ras pathway inhibition prevents neovascularization by repressing endothelial cell sprouting. J Clin Invest 2013;123:4900-8. https://doi.org/10.1172/JCI70230
  19. Devalliere J, Chang WG, Andrejecsk JW, et al. Sustained delivery of proangiogenic microRNA-132 by nanoparticle transfection improves endothelial cell transplantation. FASEB J 2014;28:908-22. https://doi.org/10.1096/fj.13-238527
  20. Choe N, Kwon JS, Kim JR, et al. The microRNA miR-132 targets Lrrfip1 to block vascular smooth muscle cell proliferation and neointimal hyperplasia. Atherosclerosis 2013;229:348-55. https://doi.org/10.1016/j.atherosclerosis.2013.05.009

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