Discovery of plasma proteins associated with ventricular fibrillation during first ST-elevation myocardial infarction via proteomics

Niels Kjær Stampe*, Maud Eline Ottenheijm, Lylia Drici, Nicolai J Wewer Albrechtsen, Annelaura Bach Nielsen, Christina Christoffersen, Peder Emil Warming, Thomas Engstrøm, Bo Gregers Winkel, Reza Jabbari, Jacob Tfelt-Hansen, Charlotte Glinge

*Corresponding author for this work

Abstract

AIMS: The underlying biological mechanisms of ventricular fibrillation (VF) during acute myocardial infarction are largely unknown. To our knowledge, this is the first proteomic study for this trait, with the aim to identify and characterize proteins that are associated with VF during first ST-elevation myocardial infarction (STEMI).

METHODS AND RESULTS: We included 230 participants from a Danish ongoing case-control study on patients with first STEMI with VF (case, n = 110) and without VF (control, n = 120) before guided catheter insertion for primary percutaneous coronary intervention. The plasma proteome was investigated using mass spectrometry-based proteomics on plasma samples collected within 24 h of symptom onset, and one patient was excluded in quality control. In 229 STEMI patients {72% men, median age 62 years [interquartile range (IQR): 54-70]}, a median of 257 proteins (IQR: 244-281) were quantified per patient. A total of 26 proteins were associated with VF; these proteins were involved in several biological processes including blood coagulation, haemostasis, and immunity. After correcting for multiple testing, two up-regulated proteins remained significantly associated with VF, actin beta-like 2 [ACTBL2, fold change (FC) 2.25, P < 0.001, q = 0.023], and coagulation factor XIII-A (F13A1, FC 1.48, P < 0.001, q = 0.023). None of the proteins were correlated with anterior infarct location.

CONCLUSION: Ventricular fibrillation due to first STEMI was significantly associated with two up-regulated proteins (ACTBL2 and F13A1), suggesting that they may represent novel underlying molecular VF mechanisms. Further research is needed to determine whether these proteins are predictive biomarkers or acute phase response proteins to VF during acute ischaemia.

Original languageEnglish
JournalEuropean heart journal. Acute cardiovascular care
Volume13
Issue number3
Pages (from-to)264-272
Number of pages9
ISSN2048-8726
DOIs
Publication statusPublished - 11 Mar 2024

Keywords

  • Blood Proteins
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention
  • Proteomics
  • ST Elevation Myocardial Infarction/complications
  • Ventricular Fibrillation/etiology

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