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Profiling of the plasma proteome across different stages of human heart failure.

ABSTRACT: Heart failure (HF) is a major public health problem characterized by inability of the heart to maintain sufficient output of blood. The systematic characterization of circulating proteins across different stages of HF may provide pathophysiological insights and identify therapeutic targets. Here we report application of aptamer-based proteomics to identify proteins associated with prospective HF incidence in a population-based cohort, implicating modulation of immunological, complement, coagulation, natriuretic and matrix remodeling pathways up to two decades prior to overt disease onset. We observe further divergence of these proteins from the general population in advanced HF, and regression after heart transplantation. By leveraging coronary sinus samples and transcriptomic tools, we describe likely cardiac and specific cellular origins for several of the proteins, including Nt-proBNP, thrombospondin-2, interleukin-18 receptor, gelsolin, and activated C5. Our findings provide a broad perspective on both cardiac and systemic factors associated with HF development.

SUBMITTER: Egerstedt A

PROVIDER: S-EPMC6925199 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Profiling of the plasma proteome across different stages of human heart failure.

Egerstedt Anna A Berntsson John J Smith Maya Landenhed ML Gidlöf Olof O Nilsson Roland R Benson Mark M Wells Quinn S QS Celik Selvi S Lejonberg Carl C Farrell Laurie L Sinha Sumita S Shen Dongxiao D Lundgren Jakob J Rådegran Göran G Ngo Debby D Engström Gunnar G Yang Qiong Q Wang Thomas J TJ Gerszten Robert E RE Smith J Gustav JG

Nature communications 20191220 1

Heart failure (HF) is a major public health problem characterized by inability of the heart to maintain sufficient output of blood. The systematic characterization of circulating proteins across different stages of HF may provide pathophysiological insights and identify therapeutic targets. Here we report application of aptamer-based proteomics to identify proteins associated with prospective HF incidence in a population-based cohort, implicating modulation of immunological, complement, coagulat ...[more]

PMID: 31862877

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Project description:Heart failure (HF) is associated with progressive ventricular remodeling and impaired contraction that affects distinctly various regions of the myocardium. Our study applied cardiac magnetic resonance (CMR) feature tracking (FT) to assess comparatively myocardial strain at 3 distinct levels: subendocardial (Endo-), mid (Myo-) and subepicardial (Epi-) myocardium across an extended spectrum of patients with HF. 59 patients with HF, divided into 3 subgroups as follows: preserved ejection fraction (HFpEF, N = 18), HF with mid-range ejection fraction (HFmrEF, N = 21), HF with reduced ejection fraction (HFrEF, N = 20) and a group of age- gender- matched volunteers (N = 17) were included. Using CMR FT we assessed systolic longitudinal and circumferential strain and strain-rate at Endo-, Myo- and Epi- levels. Strain values were the highest in the Endo- layer and progressively lower in the Myo- and Epi- layers respectively, this gradient was present in all the patients groups analyzed but decreased progressively in HFmrEF and further on in HFrEF groups. GLS decreased with the severity of the disease in all 3 layers: Normal > HFpEF > HFmrEF > HFrEF (Endo-: -23.0 ± 3.5 > -20.0 ± 3.3 > -16.4 ± 2.2 > -11.0 ± 3.2, p < 0.001, Myo-: -20.7 ± 2.4 > -17.5.0 ± 2.6 > -14.5 ± 2.1 > -9.6 ± 2.7, p < 0.001; Epi-: -15.7 ± 1.9 > -12.2 ± 2.1 > -10.6 ± 2.3 > -7.7 ± 2.3, p < 0.001). In contrast, GCS was not different between the Normal and HFpEF (Endo-: -34.5 ± 6.2 vs -33.9 ± 5.7, p = 0.51; Myo-: -21.9 ± 3.8 vs -21.3 ± 2.2, p = 0.39, Epi-: -11.4 ± 2.0 vs -10.9 ± 2.3, p = 0.54) but was, as well, markedly lower in the systolic heart failure groups: Normal > HFmrEF > HFrEF (Endo-: -34.5 ± 6.2 > -20.0 ± 4.2 > 12.3 ± 4.2, p < 0.001; Myo-: -21.9 ± 3.8 > -13.0 ± 3.4 > -8.0 ± 2.7. p < 0.001; Epi-: -11.4 ± 2.0 > -7.9 ± 2.3 > -4.5 ± 1.9. p < 0.001). CMR feature tracking multilayer strain assessment identifies large range differences between distinct myocardial regions. Our data emphasizes the importance of sub-endocardial myocardium for cardiac contraction and thus, its predilect role in imaging detection of functional impairment. CMR feature tracking offers a convenient, readily available, platform to evaluate myocardial contraction with excellent spatial resolution, rendering further details about discrete areas of the myocardium. Using this technique across distinct groups of patients with heart failure (HF), we demonstrate that subendocardial regions of the myocardium exhibit much higher strain values than mid-myocardium or subepicardial and are more sensitive to detect contractile impairment. We also show comparatively higher values of circumferential strain compared with longitudinal and a higher sensitivity to detect contractile impairment. A newly characterized group of patients, HF with mid-range ejection fraction (EF), shows similar traits of decompensation but has relatively higher strain values as patients with HF with reduced EF.

Dataset Information

Profiling of the plasma proteome across different stages of human heart failure.

Publications

Profiling of the plasma proteome across different stages of human heart failure.

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