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

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.

Automated summary

This study characterizes the plasma levels and composition of SDS-resistant aggregates (SRAs) in patients with heart failure with preserved ejection fraction (HFpEF) and identifies the molecular pathways associated with disease and/or proteostasis disruption. The study found that patients with HFpEF have higher levels of SRAs, which are composed of carbonylated and ubiquitinated proteins and enriched in proteins related to cardiovascular function/disease and proteostasis machinery. Furthermore, the study suggests that the reduced proteostasis capacity in HFpEF may contribute to the higher accumulation of SRAs.