Dataset Information

Proteomics of JHS samples identifies proteins associated with heart failure

ABSTRACT: RELEVANCE: Identifying early plasma protein biomarkers that predict the development of heart failure (HF) following myocardial infarction (MI) will help to stratify at risk subjects and provide insight into more effective therapeutic strategies. OBJECTIVE/HYPOTHESIS: The goal of this study was to determine markers of HF in African Americans, using plasma samples collected before the development of symptoms. We propose that early plasma glycoprotein changes will link to later development of heart failure. ApolipoproteinF will be the strongest indicator. METHODS: Plasma samples from a subset of Jackson Heart Study participants with a history of MI but without prevalent heart failure (HF) at visit 2 (2005-2008) were analyzed by glycoproteomics. Individuals were grouped into those who experienced subsequent HF hospitalization after visit 2 (n=15; 3 men/ 12 women) and those without HF hospitalization through 2012 (n=45; 24 men/ 21 women). N-linked plasma glycopeptides were quantified by solid-phase extraction coupled to mass spectrometry and identified using RefSeq and SwissProt. Proteins were mapped for biological processes and functional pathways using Ingenuity Pathway Analysis (IPA) and linked to clinical characteristics.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Elizabeth Flynn

LAB HEAD: Merry L Lindsey, Ph.D.

PROVIDER: PXD009870 | Pride | 2018-08-30

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	JHS_10_MI_no_HF_Male.pep.xml	Pepxml
	JHS_10_MI_no_HF_Male.prot.xml	Xml
	JHS_10_MI_no_HF_Male.raw	Raw
	JHS_11_MI_no_HF_Male.pep.xml	Pepxml
	JHS_11_MI_no_HF_Male.prot.xml	Xml

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Publications

LXR/RXR signaling and neutrophil phenotype following myocardial infarction classify sex differences in remodeling.

DeLeon-Pennell Kristine Y KY Mouton Alan J AJ Ero Osasere K OK Ma Yonggang Y Padmanabhan Iyer Rugmani R Flynn Elizabeth R ER Espinoza Ingrid I Musani Solomon K SK Vasan Ramachandran S RS Hall Michael E ME Fox Ervin R ER Lindsey Merry L ML

Basic research in cardiology 20180821 5

Sex differences in heart failure development following myocardial infarction (MI) are not fully understood. We hypothesized that differential MI signaling could explain variations in outcomes. Analysis of the mouse heart attack research tool 1.0 (422 mice; young = 5.4 ± 0.1; old = 23.3 ± 0.1 months of age) was used to dissect MI signaling pathways, which was validated in a new cohort of mice (4.8 ± 0.2 months of age); and substantiated in humans. Plasma collected at visit 2 from the MI subset of ...[more]

PMID: 30132266

Publication: 1/2

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Project description:Background: Heart failure (HF) has been recognized as global pandemic with a high rate of associated hospitalization, morbidity and mortality. Although numerous advances have been made, its representative molecular signatures remain largely unknown, especially the role of genes in HF progression. The aim of the present prospective follow-up study was to reveal potential biomarkers associated with the progression of heart failure. Methods: We collected left ventricular heart tissue from 21 HF patients and 9 healthy donors as study cohort and generated multi-level transcriptomic data. By using Masson staining to calculate the fibrosis percentage for each sample, we applied lasso regression model to identify the genes associated with fibrosis as well as progression. The genes were further validated by immunohistochemistry (IHC) staining in the same cohort and qRT-PCR using another independent cohort (20 HF and 9 healthy donors). Enzyme linked immunosorbent assay (ELISA) was used to measure the plasma level in validation cohort (87 HF patients) for predicting HF progression. Results: Based on the multi-level transcriptomic data, we examined differentially expressed genes [mRNAs, microRNAs, and long non-coding RNAs (lncRNAs)] in study cohort. The follow-up functional annotations and regulatory network reveal their potential roles in regulating extracellular matrix. We further identified several genes that were associated with fibrosis. By using the survival time before transplantation, COL1A1 was identified as a potential biomarker for HF progression and its up-regulation was confirmed by both IHC and qRT-PCR. Furthermore, COL1A1 content >281.7 ng/ml in plasma was found to be associated with poor survival within one year of heart transplantation from heart failure [Hazard Ratio (HR): 27.52, 95% Confidence Interval (CI): 7.474 to 101.3, Log-rank p-value<1.0×10-4]. Conclusions: Our results suggested that COL1A1 is a plasma biomarker of HF and associated with HF progression, especially to predict the 1-year survival from HF onset to transplantation.

Project description:After myocardial infarction (MI) activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). Interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression. Ischemic HF significantly increased the levels of serum IgM (by 5.2 fold) and IgG (by 3.6 fold) associated with remarkable content of anti-heart specificity. Comparable increase was observed in levels of circulating pro-inflammatory cytokines, such as IL-1Î² (3.8x) and TNF-Î± (6.0x). IFN-gamma was also increased in the MI group by 3.1x. However, IL-4 and IL-10 showed no significant difference between MI and sham groups. Chemokines such as MCP-1 and IL-8 were enhanced in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by the post-ischemic HF. Complement activation and immune response was among the most up-regulated processes. Interestingly, 21 out of the 101 quantified unigenes involved in inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune mediated mechanisms that act both systemically and locally. We compared RNA samples extracted from whole hearts of control and infarcted mice samples by analyzing hybridization to AECOM 32k mouse microarrays (http://microarray1k.aecom.yu.edu/) spotted with Operon version 3.0 70-mer oligonucleotides. The hybridization protocol, the slide type and the scanner settings were uniform throughout the entire experiment to minimize the technical noise. Control (sham) and infarcted red-labeled heart samples were hybridized against an in-house prepared green-labeled universal mouse reference.