Targeting pulmonary artery endothelial cells dysfunction in pulmonary arterial hypertension: in situ assessment of the effects of acute exercise

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Characterization of plasma SDS-protein aggregation profile of patients with heart failure with preserved ejection fraction

Publication . Gouveia, Marisol; Schmidt, Cristine; Teixeira, Manuel; Lopes, Mário; Aveiro, Susana; Domingues, Pedro; Xia, Ke; Colón, Wilfredo; Vitorino, Rui; Ferreira, Rita; Santos, Mário; Vieira, Sandra; Ribeiro, Fernando

This study characterizes the plasma levels and composition of SDS-resistant aggregates (SRAs) in patients with heart failure with preserved ejection fraction (HFpEF) to infer molecular pathways associated with disease and/or proteostasis disruption. Twenty adults (ten with HFpEF and ten age-matched individuals) were included. Circulating SRAs were resolved by diagonal two-dimensional SDS-PAGE, and their protein content was identified by mass spectrometry. Protein carbonylation, ubiquitination and ficolin-3 were evaluated. Patients with HFpEF showed higher SRA/total (36.6 +/- 4.9% vs 29.6 +/- 2.2%, p = 0.009) and SRA/soluble levels (58.6 +/- 12.7% vs 40.6 +/- 5.8%, p = 0.008). SRAs were carbonylated and ubiquitinated, suggesting they are composed of dysfunctional proteins resistant to degradation. SRAs were enriched in proteins associated with cardiovascular function/disease and with proteostasis machinery. Total ficolin-3 levels were decreased (0.77 +/- 0.22, p = 0.041) in HFpEF, suggesting a reduced proteostasis capacity to clear circulating SRA. Thus, the higher accumulation of SRA in HFpEF may result from a failure or overload of the protein clearance machinery.

2022Journal article

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