Gouveia Marisol, Teixeira Manuel, Schmidt Cristine, Lopes Mário, Trindade Dário, Magalhães Sandra, Henriques Ana Gabriela, Nunes Alexandra, Santos Mário, Vieira Sandra, Ribeiro Fernando
Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
Arch Med Res. 2023 Apr;54(3):211-222. doi: 10.1016/j.arcmed.2023.02.001. Epub 2023 Feb 14.
Proteostasis impairment and the consequent increase of amyloid burden in the myocardium have been associated with heart failure (HF) development and poor prognosis. A better knowledge of the protein aggregation process in biofluids could assist the development and monitoring of tailored interventions.
To compare the proteostasis status and protein's secondary structures in plasma samples of patients with HF with preserved ejection fraction (HFpEF), patients with HF with reduced ejection fraction (HFrEF), and age-matched individuals.
A total of 42 participants were enrolled in 3 groups: 14 patients with HFpEF, 14 patients with HFrEF, and 14 age-matched individuals. Proteostasis-related markers were analyzed by immunoblotting techniques. Fourier Transform Infrared (FTIR) Spectroscopy in Attenuated Total Reflectance (ATR) was applied to assess changes in the protein's conformational profile.
Patients with HFrEF showed an elevated concentration of oligomeric proteic species and reduced clusterin levels. ATR-FTIR spectroscopy coupled with multivariate analysis allowed the discrimination of HF patients from age-matched individuals in the protein amide I absorption region (1700-1600 cm), reflecting changes in protein conformation, with a sensitivity of 73 and a specificity of 81%. Further analysis of FTIR spectra showed significantly reduced random coils levels in both HF phenotypes. Also, compared to the age-matched group, the levels of structures related to fibril formation were significantly increased in patients with HFrEF, whereas the β-turns were significantly increased in patients with HFpEF.
Both HF phenotypes showed a compromised extracellular proteostasis and different protein conformational changes, suggesting a less efficient protein quality control system.
蛋白质稳态受损以及随之而来的心肌淀粉样蛋白负担增加与心力衰竭（HF）的发生发展及不良预后相关。更好地了解生物流体中的蛋白质聚集过程有助于制定和监测针对性的干预措施。
比较射血分数保留的心力衰竭（HFpEF）患者、射血分数降低的心力衰竭（HFrEF）患者以及年龄匹配个体血浆样本中的蛋白质稳态状态和蛋白质二级结构。
共纳入42名参与者，分为3组：14名HFpEF患者、14名HFrEF患者和14名年龄匹配个体。通过免疫印迹技术分析蛋白质稳态相关标志物。应用衰减全反射傅里叶变换红外（FTIR）光谱法评估蛋白质构象的变化。
HFrEF患者显示寡聚蛋白物种浓度升高，簇集素水平降低。ATR-FTIR光谱结合多变量分析能够在蛋白质酰胺I吸收区域（1700-1600 cm）区分HF患者和年龄匹配个体，反映蛋白质构象变化，灵敏度为73%，特异性为81%。对FTIR光谱的进一步分析显示，两种HF表型的无规卷曲水平均显著降低。此外，与年龄匹配组相比，HFrEF患者中与原纤维形成相关的结构水平显著增加，而HFpEF患者中的β转角显著增加。
两种HF表型均显示细胞外蛋白质稳态受损和不同的蛋白质构象变化，提示蛋白质质量控制系统效率较低。
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