Unveiling Human Proteome Signatures of Heart Failure with Preserved Ejection Fraction

Data de publicação: 01/11/2022

Autores da FMUP

• Francisca Almeida Saraiva

  Autor

• André Pedro Leite Martins Lourenço

  Autor

• António Sousa Barros

  Autor

• Francisco Aguiar Vasques Novoa Faria

  Autor

• Joaquim Adelino Correia Ferreira Leite Moreira

  Autor

• Inês Maria Falcão Sousa Pires Marques

  Autor

Participantes de fora da FMUP

• Sebastiao, MJ
• Almeida, HV
• Serra, M
• Hamdani, N
• Alves, PM
• Gomes-Alves, P

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

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent but still poorly understood clinical entity. Its current pathophysiological understanding supports a critical role of comorbidities and their chronic effect on cardiac function and structure. Importantly, despite the replication of some HFpEF phenotypic features, to this day, experimental models have failed to bring new effective therapies to the clinical setting. Thus, the direct investigation of HFpEF human myocardial samples may unveil key, and possibly human-specific, pathophysiological mechanisms. This study employed quantitative proteomic analysis by advanced mass spectrometry (SWATH-MS) to investigate signaling pathways and pathophysiological mechanisms in HFpEF. Protein-expression profiles were analyzed in human left ventricular myocardial samples of HFpEF patients and compared with a mixed control group. Functional analysis revealed several proteins that correlate with HFpEF, including those associated with mitochondrial dysfunction, oxidative stress, and inflammation. Despite the known disease heterogeneity, proteomic profiles could indicate a reduced mitochondrial oxidative phosphorylation and fatty-acid oxidation capacity in HFpEF patients with diabetes. The proteomic characterization described in this work provides new insights. Furthermore, it fosters further questions related to HFpEF cellular pathophysiology, paving the way for additional studies focused on developing novel therapies and diagnosis strategies for HFpEF patients.

Keywords

• diabetes mellitus; heart failure with preserved ejection fraction; SWATH-MS proteomics; human cardiac tissue