Display options
Share it on

Front Physiol. 2018 Feb 12;9:89. doi: 10.3389/fphys.2018.00089. eCollection 2018.

Phenotypic Modulation of Cultured Primary Human Aortic Vascular Smooth Muscle Cells by Uremic Serum.

Frontiers in physiology

Violeta Cazaña-Pérez, Pilar Cidad, Javier Donate-Correa, Ernesto Martín-Núñez, José R López-López, M Teresa Pérez-García, Teresa Giraldez, Juan F Navarro-González, Diego Alvarez de la Rosa

Affiliations

  1. Departamento de Ciencias Médicas Básicas (Fisiología), Instituto de Tecnologías Biomédicas and Centro de Investigaciones Biomédicas de Canarias, Universidad de La Laguna, Tenerife, Spain.
  2. Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain.
  3. Departamento de Bioquímica y Biología Molecular y Fisiología e Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain.

PMID: 29483881 PMCID: PMC5816230 DOI: 10.3389/fphys.2018.00089

Abstract

Patients with chronic kidney disease (CKD) have a markedly increased incidence of cardiovascular disease (CVD). The high concentration of circulating uremic toxins and alterations in mineral metabolism and hormone levels produce vascular wall remodeling and significant vascular damage. Medial calcification is an early vascular event in CKD patients and is associated to apoptosis or necrosis and trans-differentiation of vascular smooth muscle cells (VSMC) to an osteogenic phenotype. VSMC obtained from bovine or rat aorta and cultured in the presence of increased inorganic phosphate (Pi) have been extensively used to study these processes. In this study we used human aortic VSMC primary cultures to compare the effects of increased Pi to treatment with serum obtained from uremic patients. Uremic serum induced calcification, trans-differentiation and phenotypic remodeling even with normal Pi levels. In spite of similar calcification kinetics, there were fundamental differences in osteochondrogenic marker expression and alkaline phosphatase induction between Pi and uremic serum-treated cells. Moreover, high Pi induced a dramatic decrease in cell viability, while uremic serum preserved it. In summary, our data suggests that primary cultures of human VSMC treated with serum from uremic patients provides a more informative model for the study of vascular calcification secondary to CKD.

Keywords: apoptosis; chronic kidney disease; human aorta; inorganic phosphate; osteogenic differentiation; uremia; uremic serum; vascular calcification

References

  1. J Atheroscler Thromb. 2015;22(11):1197-206 - PubMed
  2. Circ Res. 1999 Feb 5;84(2):166-78 - PubMed
  3. Arterioscler Thromb Vasc Biol. 2009 May;29(5):761-6 - PubMed
  4. Circulation. 2008 Oct 21;118(17):1748-57 - PubMed
  5. Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2625-32 - PubMed
  6. Circ Res. 2000 Sep 29;87(7):E10-7 - PubMed
  7. Clin Nephrol. 2003 Jul;60 Suppl 1:S13-21 - PubMed
  8. Front Biosci (Landmark Ed). 2015 Jan 01;20:784-95 - PubMed
  9. Tissue Eng Part A. 2011 Jun;17(11-12):1561-71 - PubMed
  10. ScientificWorldJournal. 2014;2014:637065 - PubMed
  11. Int Heart J. 2012;53(5):331-5 - PubMed
  12. Arterioscler Thromb Vasc Biol. 2007 May;27(5):1030-6 - PubMed
  13. Lancet. 2012 Jan 14;379(9811):165-80 - PubMed
  14. N Engl J Med. 2007 Sep 27;357(13):1316-25 - PubMed
  15. Transpl Immunol. 1997 Dec;5(4):255-60 - PubMed
  16. Cardiovasc Pathol. 2017 Mar - Apr;27:57-67 - PubMed
  17. J Clin Invest. 1993 Apr;91(4):1800-9 - PubMed
  18. Methods Mol Biol. 2016;1430:91-105 - PubMed
  19. Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1161-70 - PubMed
  20. Cancer Res. 1988 Sep 1;48(17):4827-33 - PubMed
  21. Arterioscler Thromb Vasc Biol. 2003 Mar 1;23(3):489-94 - PubMed
  22. Annu Rev Med. 2007;58:123-39 - PubMed
  23. J Am Soc Nephrol. 2004 Dec;15(12):2959-64 - PubMed
  24. Nat Protoc. 2008;3(6):1101-8 - PubMed
  25. Nat Methods. 2012 Jul;9(7):671-5 - PubMed
  26. Kidney Int. 2013 Jun;83(6):1159-68 - PubMed
  27. Pathol Biol (Paris). 2009 Jun;57(4):318-23 - PubMed
  28. Circ Res. 2006 Apr 14;98(7):905-12 - PubMed
  29. Circ Res. 2004 Sep 17;95(6):560-7 - PubMed
  30. Circ Res. 2000 Nov 24;87(11):1055-62 - PubMed
  31. Am J Physiol Gastrointest Liver Physiol. 2004 Apr;286(4):G663-70 - PubMed
  32. Bone. 2017 Jul;100:87-93 - PubMed
  33. Am J Med. 1979 May;66(5):790-6 - PubMed
  34. J Am Soc Nephrol. 2004 Jun;15(6):1392-401 - PubMed
  35. Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1741-50 - PubMed
  36. Nephrol Dial Transplant. 2006 Dec;21(12):3435-42 - PubMed
  37. Nephrol Dial Transplant. 2006 Apr;21(4):911-6 - PubMed
  38. Kidney Int. 2006 Sep;70(6):1046-53 - PubMed
  39. Methods Mol Biol. 2016;1397:175-208 - PubMed
  40. PLoS One. 2015 Nov 10;10(11):e0141751 - PubMed
  41. Pflugers Arch. 2015 Aug;467(8):1711-22 - PubMed
  42. J Cell Biol. 1986 Dec;103(6 Pt 2):2787-96 - PubMed
  43. Semin Cell Dev Biol. 2017 Feb;62:34-49 - PubMed
  44. Int J Epidemiol. 2002 Aug;31(4):737-41 - PubMed
  45. Nephrol Dial Transplant. 2000 Feb;15(2):218-23 - PubMed
  46. Calcif Tissue Int. 2016 Nov;99(5):543-555 - PubMed
  47. Arterioscler Thromb Vasc Biol. 2011 Sep;31(9):e45-54 - PubMed

Publication Types