Pericardial Fluid Annexin A1 Is a Marker of Atrial Fibrillation in Aortic Stenosis: A Proteomics Analysis

Data de publicação: 01/02/2022 Data Ahead of Print: 11/02/2022

Autores da FMUP

• Inês Maria Falcão Sousa Pires Marques

  Autor

• Joaquim Adelino Correia Ferreira Leite Moreira

  Autor

Participantes de fora da FMUP

• Fragao-Marques, M
• Vitorino, R.
• Barroso, I
• Trindade, F

Unidades de investigação

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Atrial fibrillation (AF) is the most common arrhythmia with adverse clinical outcomes. Pericardial fluid (PF) mirrors the heart's pathophysiological status due to its proximity. This study aimed to characterise the PF proteome to identify new biomarkers of disease. Eighty-three patients submitted to aortic valve replacement surgery with severe aortic stenosis were selected, and their baseline echocardiographic and clinical variables were documented. Thirteen samples were selected blindly for proteome characterisation following a shotgun (GeLC-MS/MS) and a label-free quantification approach (LFQ). According to previous AF history, a partial least squares discriminant analysis (PLS-DA) was conducted, and the top 15 variables important in projection were identified. To inquire potential biomarkers, ROC curves were designed using LFQ data. Target proteins were further validated by ELISA, in both pericardial fluid and serum. Proteome analysis uncovered nine proteins up- and downregulated >= 2-fold. Annexin A1, annexin A2, and vimentin were among the top 15 most important variables for group discrimination in PLS-DA. Protein-protein interaction and gene ontology enrichment analysis presented functional interaction among identified proteins, which were all part of focal adhesion sites. Annexin A1 was increased in the pericardial fluid of AF patients but not in serum when quantified by ELISA. Annexin A1 is a novel pericardial fluid biomarker of AF in patients with severe aortic stenosis.

Keywords

• atrial fibrillation; aortic stenosis; cardiac surgery; biomarker; proteomics; mass spectrometry; pericardial fluid