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

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

doi:10.1007/s12265-022-10334-w

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

J Cardiovasc Transl Res. 2023 Jun;16(3):698-714. doi: 10.1007/s12265-022-10334-w. Epub 2022 Oct 21.

Authors

Marisol Gouveia¹, Cristine Schmidt^{2

3

4}, Manuel Teixeira¹, Mário Lopes⁵, Susana S Aveiro^{6

7}, Pedro Domingues⁶, Ke Xia^{8

9}, Wilfredo Colón^{8

9}, Rui Vitorino^{1

2}, Rita Ferreira¹⁰, Mário Santos^{4

11

12}, Sandra Vieira¹, Fernando Ribeiro¹³

Affiliations

¹ Department of Medical Sciences, iBiMED - Institute of Biomedicine, University of Aveiro, Aveiro, Portugal.
² Surgery and Physiology Department, Faculty of Medicine, University of Porto, Porto, Portugal.
³ Faculty of Sport, Research Center in Physical Activity, Health and Leisure, University of Porto, Porto, Portugal.
⁴ Laboratory for Integrative and Translational Research in Population Health (ITR), Porto, Portugal.
⁵ School of Health Sciences, University of Aveiro, Aveiro, Portugal.
⁶ Mass Spectrometry Centre, LAQV REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
⁷ GreenCoLab - Green Ocean Association, University of Algarve, Faro, Portugal.
⁸ Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, USA.
⁹ Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
¹⁰ QOPNA &, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
¹¹ Serviço de Cardiologia, Hospital Santo António, Centro Hospitalar Universitário Do Porto, Porto, Portugal.
¹² UMIB, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
¹³ School of Health Sciences, iBiMED - Institute of BiomedicineUniversity of AveiroAgras Do Crasto - Campus Universitário de Santiago, Building 30, 3810-193, Aveiro, Portugal. fernando.ribeiro@ua.pt.

PMID: 36271180
DOI: 10.1007/s12265-022-10334-w

Abstract

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.

Keywords: Aggregates; Bioinformatics; Cardiovascular disease; Mass spectrometry; Proteostasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Heart Failure*
Humans
Protein Aggregates
Stroke Volume

Substances

Protein Aggregates