Display options
Cite
Métrich M, Mehmeti F, Feliciano H, et al. Adrenergic Receptor Polymorphism and Maximal Exercise Capacity after Orthotopic Heart Transplantation. PLoS One. 2016;11(9):e0163475doi: 10.1371/journal.pone.0163475.
Métrich, M., Mehmeti, F., Feliciano, H., Martin, D., Regamey, J., Tozzi, P., Meyer, P., Hullin, R. (2016). Adrenergic Receptor Polymorphism and Maximal Exercise Capacity after Orthotopic Heart Transplantation. PloS one, 11(9), e0163475. https://doi.org/10.1371/journal.pone.0163475
Métrich, Mélanie, et al. "Adrenergic Receptor Polymorphism and Maximal Exercise Capacity after Orthotopic Heart Transplantation." PloS one vol. 11,9 (2016): e0163475. doi: https://doi.org/10.1371/journal.pone.0163475
Métrich M, Mehmeti F, Feliciano H, Martin D, Regamey J, Tozzi P, Meyer P, Hullin R. Adrenergic Receptor Polymorphism and Maximal Exercise Capacity after Orthotopic Heart Transplantation. PLoS One. 2016 Sep 26;11(9):e0163475. doi: 10.1371/journal.pone.0163475. eCollection 2016. PMID: 27669015; PMCID: PMC5036840.
Copy Download .nbib Format: NLM
Share it on

PLoS One. 2016 Sep 26;11(9):e0163475. doi: 10.1371/journal.pone.0163475. eCollection 2016.

Adrenergic Receptor Polymorphism and Maximal Exercise Capacity after Orthotopic Heart Transplantation.

PloS one

Mélanie Métrich, Fortesa Mehmeti, Helene Feliciano, David Martin, Julien Regamey, Piergiorgio Tozzi, Philippe Meyer, Roger Hullin,

Affiliations

  1. Cardiology, Cardiovascular Department, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
  2. Cardiology, University Hospital Geneva, University of Geneva, Geneva, Switzerland.
  3. Department of Radiology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
  4. Cardiac Surgery, Cardiovascular Department, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.

PMID: 27669015 PMCID: PMC5036840 DOI: 10.1371/journal.pone.0163475

Abstract

BACKGROUND: Maximal exercise capacity after heart transplantion (HTx) is reduced to the 50-70% level of healthy controls when assessed by cardiopulmonary exercise testing (CPET) despite of normal left ventricular function of the donor heart. This study investigates the role of donor heart β1 and β2- adrenergic receptor (AR) polymorphisms for maximal exercise capacity after orthotopic HTx.

METHODS: CPET measured peak VO2 as outcome parameter for maximal exercise in HTx recipients ≥9 months and ≤4 years post-transplant (n = 41; mean peak VO2: 57±15% of predicted value). Donor hearts were genotyped for polymorphisms of the β1-AR (Ser49Gly, Arg389Gly) and the β2-AR (Arg16Gly, Gln27Glu). Circumferential shortening of the left ventricle was measured using magnetic resonance based CSPAMM tagging.

RESULTS: Peak VO2 was higher in donor hearts expressing the β1-Ser49Ser alleles when compared with β1-Gly49 carriers (60±15% vs. 47±10% of the predicted value; p = 0.015), and by trend in cardiac allografts with the β1-AR Gly389Gly vs. β1-Arg389 (61±15% vs. 54±14%, p = 0.093). Peak VO2 was highest for the haplotype Ser49Ser-Gly389, and decreased progressively for Ser49Ser-Arg389Arg > 49Gly-389Gly > 49Gly-Arg389Arg (adjusted R2 = 0.56, p = 0.003). Peak VO2 was not different for the tested β2-AR polymorphisms. Independent predictors of peak VO2 (adjusted R2 = 0.55) were β1-AR Ser49Gly SNP (p = 0.005), heart rate increase (p = 0.016), and peak systolic blood pressure (p = 0.031). Left ventricular (LV) motion kinetics as measured by cardiac MRI CSPAMM tagging at rest was not different between carriers and non-carriers of the β1-AR Gly49allele.

CONCLUSION: Similar LV cardiac motion kinetics at rest in donor hearts carrying either β1-AR Gly49 or β1-Ser49Ser variant suggests exercise-induced desensitization and down-regulation of the β1-AR Gly49 variant as relevant pathomechanism for reduced peak VO2 in β1-AR Gly49 carriers.

Conflict of interest statement

The authors have declared that no competing interests exist.

References

  1. Eur Heart J. 1997 Nov;18(11):1823-8 - PubMed
  2. Circulation. 1988 Jul;78(1):41-8 - PubMed
  3. J Heart Lung Transplant. 2005 Nov;24(11):1710-20 - PubMed
  4. Am Heart J. 2002 Nov;144(5):840-6 - PubMed
  5. Naunyn Schmiedebergs Arch Pharmacol. 2010 Oct;382(4):357-65 - PubMed
  6. Circulation. 1990 Mar;81(3):929-38 - PubMed
  7. Pharmacogenetics. 2004 Jun;14 (6):343-9 - PubMed
  8. J Biol Chem. 2000 Jul 28;275(30):23059-64 - PubMed
  9. Transplantation. 2004 Nov 27;78(10):1523-31 - PubMed
  10. Circ Res. 1995 May;76(5):852-60 - PubMed
  11. Transplantation. 2007 Oct 27;84(8):988-96 - PubMed
  12. Pharmacol Rev. 2014 Jul;66(3):598-637 - PubMed
  13. Circ J. 2012;76(1):79-87 - PubMed
  14. J Heart Lung Transplant. 1996 Jan;15(1 Pt 1):16-24 - PubMed
  15. Mol Endocrinol. 2003 Aug;17(8):1640-6 - PubMed
  16. Cardiovasc Res. 2004 Aug 15;63(3):391-402 - PubMed
  17. J Heart Lung Transplant. 2015 Oct;34(10):1244-54 - PubMed
  18. Circulation. 1993 Sep;88(3):854-63 - PubMed
  19. Magn Reson Med. 2003 Apr;49(4):722-30 - PubMed
  20. Eur Heart J. 2006 Apr;27(7):808-16 - PubMed
  21. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11288-93 - PubMed
  22. J Heart Lung Transplant. 2003 Jan;22(1):16-27 - PubMed
  23. Pflugers Arch. 2002 Jan;443(3):370-6 - PubMed
  24. Circulation. 1999 Jul 27;100(4):361-8 - PubMed
  25. Am Heart J. 1998 Sep;136(3):465-73 - PubMed
  26. Am J Med. 2004 Oct 1;117(7):451-8 - PubMed
  27. Clin Pharmacol Ther. 2011 Mar;89(3):366-78 - PubMed
  28. J Heart Lung Transplant. 2007 Sep;26(9):915-20 - PubMed
  29. J Heart Lung Transplant. 2009 May;28(5):434-9 - PubMed
  30. Circulation. 1997 Jul 1;96(1):232-7 - PubMed
  31. Circulation. 2010 Jul 13;122(2):191-225 - PubMed
  32. Pharmacogenet Genomics. 2005 Mar;15(3):143-9 - PubMed
  33. Am J Cardiol. 2012 Oct 1;110(7):1001-7 - PubMed
  34. J Appl Physiol (1985). 2005 Nov;99(5):1776-81 - PubMed
  35. Circulation. 1990 Aug;82(2):620-3 - PubMed
  36. Magn Reson Med. 1994 Apr;31(4):401-13 - PubMed
  37. J Biol Chem. 2003 Mar 21;278(12):10784-9 - PubMed
  38. Eur J Appl Physiol Occup Physiol. 1993;66(6):500-6 - PubMed
  39. Eur J Appl Physiol. 2003 Oct;90(3-4):250-9 - PubMed
  40. Am Heart J. 2004 Jan;147(1):49-54 - PubMed
  41. J Biol Chem. 2002 Aug 23;277(34):30429-35 - PubMed
  42. Am J Transplant. 2012 Dec;12(12):3377-86 - PubMed
  43. Magn Reson Med. 1999 Dec;42(6):1048-60 - PubMed
  44. Am J Physiol Heart Circ Physiol. 2003 Nov;285(5):H2034-8 - PubMed

Publication Types