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In-depth proteomics approach reveals novel biomarkers of cardiac remodelling after myocardial infarction: An exploratory analysis.

ABSTRACT: Cardiac remodelling following myocardial infarction (MI) is a maladaptive change associated with progressive heart failure and compromises long-term clinical outcome. A substantial proportion of patients afflicted by MI still develop adverse outcomes associated with cardiac remodelling. Therefore, it is crucial to identify biomarkers for the early prediction of cardiac remodelling. An in-depth proteomics approach, including both semi-quantitative and quantitative antibody arrays, was used to identify circulating biomarkers that may be associated with detrimental cardiac remodelling. Furthermore, statistical correlation analysis was performed between the candidate biomarkers and clinical cardiac remodelling data to demonstrate their clinical utility. A systematic proteomics approach revealed that sclerostin (SOST), growth differentiation factor-15 (GDF-15), urokinase-type plasminogen activator (uPA), and midkine (MK) were increased, while monocyte chemotactic protein-3 (MCP-3) was uniquely decreased in MI patients who developed cardiac remodelling, compared to MI patients who did not develop cardiac remodelling and healthy humen. Moreover, correlation analyses between serum proteomes and cardiac remodelling echocardiographic parameters demonstrated a moderate positive association between left ventricular end-diastolic volume index (LVEDVi) and the three serum proteins, uPA, MK and GDF-15 (P < .05, respectively), and a moderate negative correlation between LV ejection fraction (LVEF) and these serum proteins (P < .05, respectively). Importantly, uPA and MK were firstly identified to be associated with the development of cardiac remodelling. The present study contributes to a better understanding of the various cytokines expressed during adverse cardiac remodelling. The identified biomarkers may facilitate early identification of patients at high risk of ischaemic heart failure pending further confirmation through larger clinical trials.

SUBMITTER: Mao S

PROVIDER: S-EPMC7520298 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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In-depth proteomics approach reveals novel biomarkers of cardiac remodelling after myocardial infarction: An exploratory analysis.

Mao Shuai S Liang Yubin Y Chen Peipei P Zhang Yuzhuo Y Yin Xin X Zhang Minzhou M

Journal of cellular and molecular medicine 20200723 17

Cardiac remodelling following myocardial infarction (MI) is a maladaptive change associated with progressive heart failure and compromises long-term clinical outcome. A substantial proportion of patients afflicted by MI still develop adverse outcomes associated with cardiac remodelling. Therefore, it is crucial to identify biomarkers for the early prediction of cardiac remodelling. An in-depth proteomics approach, including both semi-quantitative and quantitative antibody arrays, was used to ide ...[more]

PMID: 32701210

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Project description:BackgroundCardiac rupture (CR) is a rare but catastrophic mechanical complication of acute myocardial infarction (AMI) that seriously threatens human health. However, the reliable biomarkers for clinical diagnosis and the underlying signaling pathways insights of CR has yet to be elucidated.MethodsIn the present study, a quantitative approach with tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry was used to characterize the differential protein expression profiles of patients with CR. Plasma samples were collected from patients with CR (n = 37), patients with AMI (n = 47), and healthy controls (n = 47). Candidate proteins were selected for validation by multiple reaction monitoring (MRM) and enzyme-linked immunosorbent assay (ELISA).ResultsIn total, 1208 proteins were quantified and 958 differentially expressed proteins (DEPs) were identified. The difference in the expression levels of the DEPs was more noticeable between the CR and Con groups than between the AMI and Con groups. Bioinformatics analysis showed most of the DEPs to be involved in numerous crucial biological processes and signaling pathways, such as RNA transport, ribosome, proteasome, and protein processing in the endoplasmic reticulum, as well as necroptosis and leukocyte transendothelial migration, which might play essential roles in the complex pathological processes associated with CR. MRM analysis confirmed the accuracy of the proteomic analysis results. Four proteins i.e., C-reactive protein (CRP), heat shock protein beta-1 (HSPB1), vinculin (VINC) and growth/differentiation factor 15 (GDF15), were further validated via ELISA. By receiver operating characteristic (ROC) analysis, combinations of these four proteins distinguished CR patients from AMI patients with a high area under the curve (AUC) value (0.895, 95% CI, 0.802-0.988, p < 0.001).ConclusionsOur study highlights the value of comprehensive proteomic characterization for identifying plasma proteome changes in patients with CR. This pilot study could serve as a valid foundation and initiation point for elucidation of the mechanisms of CR, which might aid in identifying effective diagnostic biomarkers in the future.

Dataset Information

In-depth proteomics approach reveals novel biomarkers of cardiac remodelling after myocardial infarction: An exploratory analysis.

Publications

In-depth proteomics approach reveals novel biomarkers of cardiac remodelling after myocardial infarction: An exploratory analysis.

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