Epicardial adipose tissue volume and annexin A2/fetuin-A signalling are linked to coronary calcification in advanced coronary artery disease: Computed tomography and proteomic biomarkers from the EPICHEART study

Autores da FMUP

• Jennifer Mâncio Silva

  Autor

• António Sousa Barros

  Autor

• Glória De Fátima Almeida Conceição

  Autor

• Isabel Alexandra Marcos Miranda

  Autor

• Inês Maria Falcão Sousa Pires Marques

  Autor

• Joaquim Adelino Correia Ferreira Leite Moreira

  Autor

• Nuno Teodoro V. Reis Bettencourt Sousa

  Autor

Participantes de fora da FMUP

• Pessoa Amorim, G
• Santa, C
• Bartosch, C
• Ferreira, W
• Carvalho, M
• Ferreira, N
• Vouga, L
• Vitorino, R.
• Manadas, B
• Ribeiro, VG

Unidades de investigação

• Cirurgia e Fisiologia

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Background & aims: The role of epicardial adipose tissue (EAT) in the pathophysiology of late stage-coronary artery disease (CAD) has not been investigated. We explored the association of EAT volume and its proteome with advanced coronary atherosclerosis. Methods: The EPICHEART Study prospectively enrolled 574 severe aortic stenosis patients referred to cardiac surgery. Before surgery, EAT volume was quantified by computed tomography (CT). During surgery, epicardial, mediastinal (MAT) and subcutaneous (SAT) adipose tissue samples were collected to explore fat phenotype by analyzing the proteomic profile using SWATH-mass spectrometry; pericardial fluid and peripheral venous blood were also collected. CAD presence was defined as coronary artery stenosis >= 50% in invasive angiography and by CT-derived Agatston coronary calcium score (CCS). Results: EAT volume adjusted for body fat was associated with higher CCS, but not with the presence of coronary stenosis. In comparison with mediastinal and subcutaneous fat depots, EAT exhibited a pro-calcifying proteomic profile in patients with CAD characterized by upregulation of annexin-A2 and downregulation of fetuin-A; annexin-A2 protein levels in EAT samples were also positively correlated with CCS. We confirmed that the annexin-A2 gene was overexpressed in EAT samples of CAD patients and positively correlated with CCS. Fetuin-A gene was not detected in EAT samples, but systemic fetuin-A was higher in CAD than in non-CAD patients, suggesting that fetuin-A was locally downregulated. Conclusions: In an elderly cohort of stable patients, CCS was associated with EAT volume and annexin-A2/fetuin-A signaling, suggesting that EAT might orchestrate pro-calcifying conditions in the late phases of CAD.

Copyright © 2019 Elsevier B.V. All rights reserved.

Keywords

• Epicardial adipose tissue; Epicardial fat; Coronary calcification; Coronary atherosclerosis; Cardiac computed tomography; Proteomics; Mass spectrometry; EPICHEART study