Urinary proteomic signatures associated with β-blockade and heart rate in heart transplant recipients

PLoS One. 2018 Sep 24;13(9):e0204439. doi: 10.1371/journal.pone.0204439. eCollection 2018.

Abstract

Objectives: Heart transplant (HTx) recipients have a high heart rate (HR), because of graft denervation and are frequently started on β-blockade (BB). We assessed whether BB and HR post HTx are associated with a specific urinary proteomic signature.

Methods: In 336 HTx patients (mean age, 56.8 years; 22.3% women), we analyzed cross-sectional data obtained 7.3 years (median) after HTx. We recorded medication use, measured HR during right heart catheterization, and applied capillary electrophoresis coupled with mass spectrometry to determine the multidimensional urinary classifiers HF1 and HF2 (known to be associated with left ventricular dysfunction), ACSP75 (acute coronary syndrome) and CKD273 (renal dysfunction) and 48 sequenced urinary peptides revealing the parental proteins.

Results: In adjusted analyses, HF1, HF2 and CKD273 (p ≤ 0.024) were higher in BB users than non-users with a similar trend for ACSP75 (p = 0.06). Patients started on BB within 1 year after HTx and non-users had similar HF1 and HF2 levels (p ≥ 0.098), whereas starting BB later was associated with higher HF1 and HF2 compared with non-users (p ≤ 0.014). There were no differences in the urinary biomarkers (p ≥ 0.27) according to HR. BB use was associated with higher urinary levels of collagen II and III fragments and non-use with higher levels of collagen I fragments.

Conclusions: BB use, but not HR, is associated with a urinary proteomic signature that is usually associated with worse outcome, because unhealthier conditions probably lead to initiation of BB. Starting BB early after HTx surgery might be beneficial.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Biomarkers / urine
  • Catheterization
  • Cross-Sectional Studies
  • Female
  • Heart Rate* / physiology
  • Heart Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Peptides / urine*
  • Proteome*
  • Proteomics
  • Sensitivity and Specificity

Substances

  • Adrenergic beta-Antagonists
  • Biomarkers
  • Peptides
  • Proteome

Grant support

The European Union (HEALTH-F7-305507 HOMAGE; URL: http://www.homage-hf.eu/) and the European Research Council (Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET; URL: http://cordis.europa.eu/project/rcn/104182_en.html and http://cordis.europa.eu/project/rcn/205861_en.html), the European Research Area Net for Cardiovascular Diseases (JTC2017-046-PROACT; URL: http://www.era-cvd.eu/), and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13; URL: http://www.fwo.be/) currently support the Studies Coor-dinating Centre in Leuven. Dr. Harald Mischak and Esther Nkuipou-Kenfack received support from the European Commission via the SysVasc project (HEALTH FP7-603288; URL: https://cordis.europa.eu/project/rcn/111200_en.html). Dr. Jan Van Keer is the recipient of a PhD researcher scholarship granted by the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (11B3618N; URL: http://www.fwo.be/en/). The funder provided support in the form of salaries for authors (QFH, JVK, ZYZ, ST, WYY, LT, FFW, JAS), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.