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Lymphocyte levels of GRK2 (betaARK1) mirror changes in the LVAD-supported failing human heart: lower GRK2 associated with improved beta-adrenergic signaling after mechanical unloading.

Publication ,  Journal Article
Hata, JA; Williams, ML; Schroder, JN; Lima, B; Keys, JR; Blaxall, BC; Petrofski, JA; Jakoi, A; Milano, CA; Koch, WJ
Published in: J Card Fail
June 2006

BACKGROUND: In human heart failure, increased expression of G protein-coupled receptor kinases (GRKs) causes the loss of beta-adrenergic receptor (betaAR) signaling and function. Mechanical unloading with a left ventricular assist device (LVAD) promotes reverse remodeling, which includes restoration of betaAR responsiveness. We tested the hypothesis that LVAD support of the failing human heart alters the expression and activity of GRKs and we sought to determine whether changes in myocardial GRKs could be tracked in lymphocytes. METHODS AND RESULTS: Paired samples of human LV tissue (n = 12) and blood were obtained at the time of LVAD implantation (heart failure) and subsequent cardiac transplantation (LVAD). betaAR signaling was quantified by receptor density and adenylyl cyclase activity. Immunoblotting and real-time reverse transcription polymerase chain reaction were used to measure GRK2 and GRK5 protein and mRNA levels. Rhodopsin phosphorylation was used to assess total GRK activity. Consistent with reverse remodeling, betaAR density and signaling were restored to nonfailing levels after LVAD support. GRK2 protein levels were significantly reduced 55% after LVAD support and GRK2 mRNA was similarly reduced. In contrast, GRK5 protein and mRNA levels were unchanged. Total myocardial GRK activity was reduced similar to the drop in GRK2 expression. In lymphocytes, GRK2 protein levels were decreased after LVAD support and there was a significant positive correlation between myocardial and lymphocyte GRK2 levels in both heart failure and LVAD samples. CONCLUSION: The changes in myocardial GRK2 expression and activity that are mirrored in lymphocytes provide a possible mechanism for the restoration of betaAR signaling and reverse remodeling after mechanical unloading in the failing heart. Moreover, lymphocytes may provide a surrogate marker of myocardial GRK2 in these patients.

Duke Scholars

Published In

J Card Fail

DOI

EISSN

1532-8414

Publication Date

June 2006

Volume

12

Issue

5

Start / End Page

360 / 368

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Myocardium
  • Middle Aged
  • Male
  • Lymphocytes
  • Humans
  • Heart-Assist Devices
  • Heart
 

Citation

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Hata, J. A., Williams, M. L., Schroder, J. N., Lima, B., Keys, J. R., Blaxall, B. C., … Koch, W. J. (2006). Lymphocyte levels of GRK2 (betaARK1) mirror changes in the LVAD-supported failing human heart: lower GRK2 associated with improved beta-adrenergic signaling after mechanical unloading. J Card Fail, 12(5), 360–368. https://doi.org/10.1016/j.cardfail.2006.02.011
Hata, Jonathan A., Matthew L. Williams, Jacob N. Schroder, Brian Lima, Janelle R. Keys, Burns C. Blaxall, Jason A. Petrofski, Andre Jakoi, Carmelo A. Milano, and Walter J. Koch. “Lymphocyte levels of GRK2 (betaARK1) mirror changes in the LVAD-supported failing human heart: lower GRK2 associated with improved beta-adrenergic signaling after mechanical unloading.J Card Fail 12, no. 5 (June 2006): 360–68. https://doi.org/10.1016/j.cardfail.2006.02.011.
Hata, Jonathan A., et al. “Lymphocyte levels of GRK2 (betaARK1) mirror changes in the LVAD-supported failing human heart: lower GRK2 associated with improved beta-adrenergic signaling after mechanical unloading.J Card Fail, vol. 12, no. 5, June 2006, pp. 360–68. Pubmed, doi:10.1016/j.cardfail.2006.02.011.
Hata JA, Williams ML, Schroder JN, Lima B, Keys JR, Blaxall BC, Petrofski JA, Jakoi A, Milano CA, Koch WJ. Lymphocyte levels of GRK2 (betaARK1) mirror changes in the LVAD-supported failing human heart: lower GRK2 associated with improved beta-adrenergic signaling after mechanical unloading. J Card Fail. 2006 Jun;12(5):360–368.
Journal cover image

Published In

J Card Fail

DOI

EISSN

1532-8414

Publication Date

June 2006

Volume

12

Issue

5

Start / End Page

360 / 368

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Myocardium
  • Middle Aged
  • Male
  • Lymphocytes
  • Humans
  • Heart-Assist Devices
  • Heart