Gouveia, MarisolSchmidt, CristineBasilio, Priscilla GoisAveiro, SusanaDomingues, PedroXia, KeColón, WilfredoVitorino, RuiFerreira, RitaSantos, MárioVieira, Sandra I.Ribeiro, Fernando2023-11-282023-11-282023-101863-9704http://hdl.handle.net/10400.1/20173BackgroundHeart failure (HF) often disrupts the protein quality control (PQC) system leading to protein aggregate accumulation. Evidence from tissue biopsies showed that exercise restores PQC system in HF; however, little is known about its effects on plasma proteostasis.AimTo determine the effects of exercise training on the load and composition of plasma SDS-resistant protein aggregates (SRA) in patients with HF with reduced ejection fraction (HFrEF).MethodsEighteen patients with HFrEF (age: 63.4 +/- 6.5 years; LVEF: 33.4 +/- 11.6%) participated in a 12-week combined (aerobic plus resistance) exercise program (60 min/session, twice per week). The load and content of circulating SRA were assessed using D2D SDS-PAGE and mass spectrometry. Cardiorespiratory fitness, quality of life, and circulating levels of high-sensitive C-reactive protein, N-terminal pro-B-type natriuretic peptide (NT-proBNP), haptoglobin and ficolin-3, were also evaluated at baseline and after the exercise program.ResultsThe exercise program decreased the plasma SRA load (% SRA/total protein: 38.0 +/- 8.9 to 36.1 +/- 9.7%, p = 0.018; % SRA/soluble fraction: 64.3 +/- 27.1 to 59.8 +/- 27.7%, p = 0.003). Plasma SRA of HFrEF patients comprised 31 proteins, with alpha-2-macroglobulin and haptoglobin as the most abundant ones. The exercise training significantly increased haptoglobin plasma levels (1.03 +/- 0.40 to 1.11 +/- 0.46, p = 0.031), while decreasing its abundance in SRA (1.83 +/- 0.54 x 1011 to 1.51 +/- 0.59 x 1011, p = 0.049). Cardiorespiratory fitness [16.4(5.9) to 19.0(5.2) ml/kg/min, p = 0.002], quality of life, and circulating NT-proBNP [720.0(850.0) to 587.0(847.3) pg/mL, p = 0.048] levels, also improved after the exercise program.ConclusionExercise training reduced the plasma SRA load and enhanced PQC, potentially via haptoglobin-mediated action, while improving cardiorespiratory fitness and quality of life of patients with HFrEF.engHFrEFExercise trainingProtein aggregatesProteomicsjournal article10.1007/s11010-023-04884-z1573-4919