Characterization of Plasma SDS-Protein Aggregation Profile of Patients with Heart Failure with Preserved Ejection Fraction

Journal of Cardiovascular Translational Research

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

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.

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