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Proteomics of acute heart failure in a rat post-myocardial infarction model.

ABSTRACT: The aim of the present study was to identify the mechanisms underlying the development of post-myocardial infarction (post-MI) heart failure. The left anterior descending coronary artery of rats was occluded to mimic human ischemic heart disease. Linear Trap Quadropole OrbiTrap mass spectrometry was used to profile the expressions of energy metabolism?associated and calcium?binding proteins in the post?MI and control groups. Using the online Protein Analysis Through Evolutionary Relationships classification system, 78 differentially expressed proteins were identified, including 50 downregulated proteins and 28 upregulated proteins in post?MI group when compared with the control group. The differentially expressed proteins were closely associated with energy metabolism, contractile function, calcium handling, pathological hypertrophy and cardiac remodeling. These results were further validated using western blotting. At different postoperative time points (1st and 14th day following surgery) during the progression of advanced heart failure post?MI, dynamic alterations in differential protein expression were identified. The expression of the vitamin D protein was significantly upregulated on the 1st day post?MI however, was then downregulated with progression of the disease on the 14th day post?MI. These results identified various target proteins associated with the disease, which may be used as diagnostic markers.

SUBMITTER: Guo Y

PROVIDER: S-EPMC5561871 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Proteomics of acute heart failure in a rat post-myocardial infarction model.

Guo Yichen Y Cui Lianqun L Jiang Shiliang S Zhang Airong A Jiang Shu S

Molecular medicine reports 20170620 2

The aim of the present study was to identify the mechanisms underlying the development of post-myocardial infarction (post-MI) heart failure. The left anterior descending coronary artery of rats was occluded to mimic human ischemic heart disease. Linear Trap Quadropole OrbiTrap mass spectrometry was used to profile the expressions of energy metabolism‑associated and calcium‑binding proteins in the post‑MI and control groups. Using the online Protein Analysis Through Evolutionary Relationships cl ...[more]

PMID: 28656274

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Project description:BackgroundHeart failure (HF) is the most common long-term complication of acute myocardial infarction (MI). Understanding plasma proteins associated with post-MI HF and their gene expression may identify new candidates for biomarker and drug target discovery.MethodsWe used aptamer-based affinity-capture plasma proteomics to measure 1305 plasma proteins at 1 month post-MI in a New Zealand cohort (CDCS [Coronary Disease Cohort Study]) including 181 patients post-MI who were subsequently hospitalized for HF in comparison with 250 patients post-MI who remained event free over a median follow-up of 4.9 years. We then correlated plasma proteins with left ventricular ejection fraction measured at 4 months post-MI and identified proteins potentially coregulated in post-MI HF using weighted gene co-expression network analysis. A Singapore cohort (IMMACULATE [Improving Outcomes in Myocardial Infarction through Reversal of Cardiac Remodelling]) of 223 patients post-MI, of which 33 patients were hospitalized for HF (median follow-up, 2.0 years), was used for further candidate enrichment of plasma proteins by using Fisher meta-analysis, resampling-based statistical testing, and machine learning. We then cross-referenced differentially expressed proteins with their differentially expressed genes from single-cell transcriptomes of nonmyocyte cardiac cells isolated from a murine MI model, and single-cell and single-nucleus transcriptomes of cardiac myocytes from murine HF models and human patients with HF.ResultsIn the CDCS cohort, 212 differentially expressed plasma proteins were significantly associated with subsequent HF events. Of these, 96 correlated with left ventricular ejection fraction measured at 4 months post-MI. Weighted gene co-expression network analysis prioritized 63 of the 212 proteins that demonstrated significantly higher correlations among patients who developed post-MI HF in comparison with event-free controls (data set 1). Cross-cohort meta-analysis of the IMMACULATE cohort identified 36 plasma proteins associated with post-MI HF (data set 2), whereas single-cell transcriptomes identified 15 gene-protein candidates (data set 3). The majority of prioritized proteins were of matricellular origin. The 6 most highly enriched proteins that were common to all 3 data sets included well-established biomarkers of post-MI HF: N-terminal B-type natriuretic peptide and troponin T, and newly emergent biomarkers, angiopoietin-2, thrombospondin-2, latent transforming growth factor-β binding protein-4, and follistatin-related protein-3, as well.ConclusionsLarge-scale human plasma proteomics, cross-referenced to unbiased cardiac transcriptomics at single-cell resolution, prioritized protein candidates associated with post-MI HF for further mechanistic and clinical validation.

Dataset Information

Proteomics of acute heart failure in a rat post-myocardial infarction model.

Publications

Proteomics of acute heart failure in a rat post-myocardial infarction model.

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