Coronary Artery Disease and Aortic Valve Stenosis: A Urine Proteomics Study

Data de publicação: 01/11/2022 Data Ahead of Print: 05/11/2022

Autores da FMUP

• António Sousa Barros

  Autor

• Inês Maria Falcão Sousa Pires Marques

  Autor

• Joaquim Adelino Correia Ferreira Leite Moreira

  Autor

Participantes de fora da FMUP

• Perpetuo, L
• Dalsuco, J
• Nogueira Ferreira, R
• Resende Goncalves, P
• Ferreira, R
• Trindade, F
• Vitorino, R.

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

Coronary artery disease (CAD) and the frequently coexisting aortic valve stenosis (AVS) are heart diseases accounting for most cardiac surgeries. These share many risk factors, such as age, diabetes, hypertension, or obesity, and similar pathogenesis, including endothelial disruption, lipid and immune cell infiltration, inflammation, fibrosis, and calcification. Unsuspected CAD and AVS are sometimes detected opportunistically through echocardiography, coronary angiography, and magnetic resonance. Routine biomarkers for early detection of either of these atherosclerotic-rooted conditions would be important to anticipate the diagnosis. With a noninvasive collection, urine is appealing for biomarker assessment. We conducted a shotgun proteomics exploratory analysis of urine from 12 CAD and/or AVS patients and 11 controls to identify putative candidates to differentiate these diseases from healthy subjects. Among the top 20 most dysregulated proteins, TIMP1, MMP2 and vWF stood out, being at least 2.5x increased in patients with CAD/AVS and holding a central position in a network of protein-protein interactions. Moreover, their assessment in an independent cohort (19 CAD/AVS and 10 controls) evidenced strong correlations between urinary TIMP1 and vWF levels and a common cardiovascular risk factor - HDL (r = 0.59, p < 0.05, and r = 0.64, p < 0.01, respectively).

Keywords

• coronary artery disease; aortic valve stenosis; biomarkers; urine; proteomics