Dataset Information

Dysregulated circulating SOCS3 and haptoglobin expression associated with stable coronary artery disease and acute coronary syndrome: An integrated study based on bioinformatics analysis and case-control validation.

ABSTRACT: OBJECTIVE:To extensively use blood transcriptome analysis to identify potential diagnostic and therapeutic targets for cardiovascular diseases. METHODS:Two gene expression datasets (GSE59867 and GSE62646) were downloaded from GEO DataSets to identify altered blood transcriptomes in patients with ST-segment elevation myocardial infarction (STEMI) compared to stable coronary artery disease (CAD). Thereafter, several computational approaches were taken to determine functional roles and regulatory networks of differentially expressed genes (DEGs). Finally, the expression of dysregulated two hub genes-suppressor of cytokine signaling 3 (SOCS3) and haptoglobin (HP)-were validated in a case-control study. RESULTS:A total of 119 DEGs were identified in the discovery phase, consisting of 71 downregulated genes and 48 upregulated genes; two hub modules consisting of two hub genes-SOCS3 and HP-were identified. In the validation phase, both SOCS3 and HP were significantly downregulated in the stable CAD and acute coronary syndrome (ACS) patients when compared with healthy controls. Meanwhile, HP was significantly upregulated in STEMI patients when compared with stable CAD patients (p=0.041). Logistic regression analysis indicated that: downregulated expression of HP correlated with increased risk of CAD [odds ratio (OR)=0.52, 95% confidence interval (CI)=0.31~0.87, p=0.013]; and downregulated expression of SOCS3 correlated with increased risk of ACS (OR=0.66, 95% CI=0.46~0.94, p=0.023) when age, gender, history of hyperlipidemia, diabetes and hypertension were included as covariates. CONCLUSION:Future clarification of how SOCS3 and HP influence the pathogenesis of disease may pave the way for the development of novel diagnostic and therapeutic methods.

SUBMITTER: Zhang X

PROVIDER: S-EPMC7585973 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Dysregulated circulating SOCS3 and haptoglobin expression associated with stable coronary artery disease and acute coronary syndrome: An integrated study based on bioinformatics analysis and case-control validation.

Zhang Xunnan X Lv Xi X Li Xiandong X Wang Yaping Y Lin Hao-Yu HY Zhang Jicai J Peng Chunyan C

Anatolian journal of cardiology 20200901 3

<h4>Objective</h4>To extensively use blood transcriptome analysis to identify potential diagnostic and therapeutic targets for cardiovascular diseases.<h4>Methods</h4>Two gene expression datasets (GSE59867 and GSE62646) were downloaded from GEO DataSets to identify altered blood transcriptomes in patients with ST-segment elevation myocardial infarction (STEMI) compared to stable coronary artery disease (CAD). Thereafter, several computational approaches were taken to determine functional roles a ...[more]

PMID: 32870172

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Project description:Exosomal miRNAs are currently being explored as a novel class of biomarkers in cardiovascular diseases. However, few reports have focused on the value of circulating exosomal miRNAs as biomarkers for stable coronary artery disease (SCAD). Here, we aimed to investigate whether miRNAs involved in cardiovascular diseases in circulating exosomes could serve as novel diagnostic biomarkers for SCAD. Firstly, the serum exosomes were isolated and purified by the ExoQuick reagent and identified by transmission electron microscopy, western blot, and nanoparticle tracking analysis. Then, the purified exosomes were quantified by measuring the exosome protein concentration and calculating the total protein amount. Next, eight miRNAs involved in cardiovascular diseases, miR-192-5p, miR-148b-3p, miR-125a-3p, miR-942-5p, miR-149-5p, miR-32-5p, miR-144-3p, and miR-142-5p, were quantified in circulating exosomes from the control group (n = 20) and the SCAD group (n = 20) by quantitative real-time polymerase chain reaction (qPCR). Finally, the gene targets of the differentially expressed miRNAs were predicted, and the functions and signaling pathways of these targets were analyzed using an online database. The isolated exosomes had a bilayer membrane with a diameter of about 100 nm and expressed exosomal markers including CD63, Tsg101, and Flotillin but negatively expressed Calnexin. Both the exosome protein concentration and total protein amount exhibited no significant differences between the two groups. The qPCR assay demonstrated that among the eight miRNAs, the expression levels of miR-942-5p, miR-149-5p, and miR-32-5p in the serum exosomes from the SCAD group were significantly higher than that from the control group. And the three miRNAs for SCAD diagnosis exhibited AUC values of 0.693, 0.702, and 0.691, respectively. GO categories and signaling pathways analysis showed that some of the predictive targets of these miRNAs were involved in the pathophysiology processes of SCAD. In conclusion, our findings suggest that serum exosomal miR-942-5p, miR-149-5p, and miR-32-5p may serve as potential diagnostic biomarkers for SCAD.

Project description:BACKGROUND:It is suggested that the integration of maximal myocardial blood flow (MBF) and coronary flow reserve (CFR), termed coronary flow capacity, allows for comprehensive evaluation of patients with known or suspected stable coronary artery disease. Because management decisions are predicated on clinical risk, we sought to determine the independent and integrated value of maximal MBF and CFR for predicting cardiovascular death. METHODS:MBF and CFR were quantified in 4029 consecutive patients (median age 66 years, 50.5% women) referred for rest/stress myocardial perfusion positron emission tomography scans from January 2006 to December 2013. The primary outcome was cardiovascular mortality. Maximal MBF <1.8 mL·g-1·min-1 and CFR<2 were considered impaired. Four patient groups were identified based on the concordant or discordant impairment of maximal MBF or CFR. Association of maximal MBF and CFR with cardiovascular death was assessed using Cox and Poisson regression analyses. RESULTS:A total of 392 (9.7%) cardiovascular deaths occurred over a median follow-up of 5.6 years. CFR was a stronger predictor of cardiovascular mortality than maximal MBF beyond traditional cardiovascular risk factors, left ventricular ejection fraction, myocardial scar and ischemia, rate-pressure product, type of radiotracer or stress agent used, and revascularization after scan (adjusted hazard ratio, 1.79; 95% confidence interval [CI], 1.38-2.31; P<0.001 per unit decrease in CFR after adjustment for maximal MBF and clinical covariates; and adjusted hazard ratio, 1.03; 95% CI, 0.84-1.27; P=0.8 per unit decrease in maximal MBF after adjustment for CFR and clinical covariates). In univariable analyses, patients with concordant impairment of CFR and maximal MBF had high cardiovascular mortality of 3.3% (95% CI, 2.9-3.7) per year. Patients with impaired CFR but preserved maximal MBF had an intermediate cardiovascular mortality of 1.7% (95% CI, 1.3-2.1) per year. These patients were predominantly women (70%). Patients with preserved CFR but impaired maximal MBF had low cardiovascular mortality of 0.9% (95% CI, 0.6-1.6) per year. Patients with concordantly preserved CFR and maximal MBF had the lowest cardiovascular mortality of 0.4% (95 CI, 0.3-0.6) per year. In multivariable analysis, the cardiovascular mortality risk gradient across the 4 concordant or discordant categories was independently driven by impaired CFR irrespective of impairment in maximal MBF. CONCLUSIONS:CFR is a stronger predictor of cardiovascular mortality than maximal MBF. Concordant and discordant categories based on integrating CFR and maximal MBF identify unique prognostic phenotypes of patients with known or suspected coronary artery disease.

Dataset Information

Dysregulated circulating SOCS3 and haptoglobin expression associated with stable coronary artery disease and acute coronary syndrome: An integrated study based on bioinformatics analysis and case-control validation.

Publications

Dysregulated circulating SOCS3 and haptoglobin expression associated with stable coronary artery disease and acute coronary syndrome: An integrated study based on bioinformatics analysis and case-control validation.

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