Dataset Information

Circulating Cell and Plasma microRNA Profiles Differ between Non-ST-Segment and ST-Segment-Elevation Myocardial Infarction.

ABSTRACT: BACKGROUND:Differences in plasma and whole blood expression microRNAs (miRNAs) in patients with an acute coronary syndrome (ACS) have been determined in both in vitro and in vivo studies. Although most circulating miRNAs are located in the cellular components of whole blood, little is known about the miRNA profiles of whole blood subcomponents, including plasma, platelets and leukocytes in patients with myocardial ischemia. METHODS:Thirteen patients with a ST-segment-elevation (STEMI) or non-ST-segment elevation (NSTEMI) myocardial infarction were identified in the University of Massachusetts Medical Center Emergency Department (ED) or cardiac catheterization laboratory between February and June of 2012. Whole blood was obtained from arterial blood samples at the time of cardiac catheterization and cell-specific miRNA profiling was performed. Expression of 343 miRNAs was quantified from whole blood, plasma, platelets, and peripheral blood mononuclear cells using a high-throughput, quantitative Real-Time polymerase-chain reaction system (qRT-PCR). RESULTS:MiRNAs associated with STEMI as compared to NSTEMI patients included miR-25-3p, miR-221-3p, and miR-374b-5p. MiRNA 30d-5p was associated with plasma, platelets, and leukocytes in both STEMI and NSTEMI patients; miRNAs 221-3p and 483-5p were correlated with plasma and platelets only in NSTEMI patients. CONCLUSIONS:Cell-specific miRNA profiles differed between patients with STEMI and NSTEMI. The miRNA distribution is also unique amongst plasma, platelets, and leukocytes in patients with ischemic heart disease or ACS. Our findings suggest unique miRNA profiles among the circulating subcomponents in patients presenting with myocardial ischemia.

SUBMITTER: Ward JA

PROVIDER: S-EPMC3890357 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Circulating Cell and Plasma microRNA Profiles Differ between Non-ST-Segment and ST-Segment-Elevation Myocardial Infarction.

Ward Jeanine A JA Esa Nada N Pidikiti Rahul R Freedman Jane E JE Keaney John F JF Tanriverdi Kahraman K Vitseva Olga O Ambros Victor V Lee Rosalind R McManus David D DD

Family medicine & medical science research 20131001 2

<h4>Background</h4>Differences in plasma and whole blood expression microRNAs (miRNAs) in patients with an acute coronary syndrome (ACS) have been determined in both in vitro and in vivo studies. Although most circulating miRNAs are located in the cellular components of whole blood, little is known about the miRNA profiles of whole blood subcomponents, including plasma, platelets and leukocytes in patients with myocardial ischemia.<h4>Methods</h4>Thirteen patients with a ST-segment-elevation (ST ...[more]

PMID: 24432306

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Project description:BackgroundCirculating microRNAs (miRNAs) have been found to have different expressions in different phases of acute myocardial infarction. The profiles of plasma exosome miRNAs in patients with ST-segment elevation myocardial infarction (STEMI) at 3-6 months postinfarction are unknown.ObjectiveThe aim of this study was to assess the profiles of plasma exosome miRNAs in patients with STEMI in comparison with healthy volunteers and to select specific exosome miRNAs related to pathophysiological changes post-STEMI.MethodsPlasma and echocardiography parameters were collected from 30 patients 3-6 months after STEMI and 30 healthy volunteers. Plasma exosome miRNAs were assessed by using high-throughput sequence (Illumina HiSeq 2500) and profile of the plasma exosome miRNAs was established in 10 patients and 6 healthy volunteers. The specific exosome miRNAs related to heart diseases were selected according to the TargetScan database. The specificity of the selected exosome miRNAs was evaluated in additional 20 post-STEMI patients and 24 healthy volunteers by using quantitative PCR (qPCR). Left ventricular remodeling (LVR) was defined using the European Association of Cardiovascular Imaging criteria according to echocardiography examination. Correlations between expression of the specific miRNAs and echocardiography parameters of LVR were assessed using the Spearman correlation analysis.ResultsTwenty eight upregulated miRNAs and 49 downregulated miRNAs were found in patients 3-6 months after STEMI (p < 0.01) in comparison with the healthy volunteers. The two least expressed and heart-related exosome miRNAs were hsa-miR-181a-3p (0.64-fold, p < 0.01) and hsa-miR-874-3p (0.50-fold, p < 0.01), which were further confirmed by using qPCR and demonstrated significant specificity in another 20 patients with post-STEMI comparing to 24 healthy volunteers [area under the curve (AUC) = 0.68, p < 0.05; AUC = 0.74, p < 0.05]. The expression of hsa-miR-181a-3p was downregulated in patients with LV adverse remodeling in comparison with patients without LV adverse remodeling and healthy volunteers.ConclusionCirculating exosome miR-874-3p and miR-181a-3p were downregulated in patients with STEMI postinfarction. Exosome hsa-miR-181a-3p might play a potential role in the development of LVR in patients with post-STEMI.

Project description:ImportanceChallenges to improving ST-segment elevation myocardial infarction (STEMI) care are formidable in low- to middle-income countries because of several system-level factors.ObjectiveTo examine access to reperfusion and percutaneous coronary intervention (PCI) during STEMI using a hub-and-spoke model.Design, setting, and participantsThis multicenter, prospective, observational study of a quality improvement program studied 2420 patients 20 years or older with symptoms or signs consistent with STEMI at primary care clinics, small hospitals, and PCI hospitals in the southern state of Tamil Nadu in India. Data were collected from the 4 clusters before implementation of the program (preimplementation data). We required a minimum of 12 weeks for the preimplementation data with the period extending from August 7, 2012, through January 5, 2013. The program was then implemented in a sequential manner across the 4 clusters, and data were collected in the same manner (postimplementation data) from June 12, 2013, through June 24, 2014, for a mean 32-week period.ExposuresCreation of an integrated, regional quality improvement program that linked the 35 spoke health care centers to the 4 large PCI hub hospitals and leveraged recent developments in public health insurance schemes, emergency medical services, and health information technology.Main outcomes and measuresPrimary outcomes focused on the proportion of patients undergoing reperfusion, timely reperfusion, and postfibrinolysis angiography and PCI. Secondary outcomes were in-hospital and 1-year mortality.ResultsA total of 2420 patients with STEMI (2034 men [84.0%] and 386 women [16.0%]; mean [SD] age, 54.7 [12.2] years) (898 in the preimplementation phase and 1522 in the postimplementation phase) were enrolled, with 1053 patients (43.5%) from the spoke health care centers. Missing data were common for systolic blood pressure (213 [8.8%]), heart rate (223 [9.2%]), and anterior MI location (279 [11.5%]). Overall reperfusion use and times to reperfusion were similar (795 [88.5%] vs 1372 [90.1%]; P = .21). Coronary angiography (314 [35.0%] vs 925 [60.8%]; P < .001) and PCI (265 [29.5%] vs 707 [46.5%]; P < .001) were more commonly performed during the postimplementation phase. In-hospital mortality was not different (52 [5.8%] vs 85 [5.6%]; P = .83), but 1-year mortality was lower in the postimplementation phase (134 [17.6%] vs 179 [14.2%]; P = .04), and this difference remained consistent after multivariable adjustment (adjusted odds ratio, 0.76; 95% CI, 0.58-0.98; P = .04).Conclusions and relevanceA hub-and-spoke model in South India improved STEMI care through greater use of PCI and may improve 1-year mortality. This model may serve as an example for developing STEMI systems of care in other low- to middle-income countries.

Project description:Objective This study is aimed at exploring the underlying molecular mechanisms of ST-segment elevation myocardial infarction (STEMI) and provides potential clinical prognostic biomarkers for STEMI. Methods The GSE60993 dataset was downloaded from the GEO database, and the differentially expressed genes (DEGs) between STEMI and control groups were screened. Enrichment analysis of the DEGs was subsequently performed using the DAVID database. A protein–protein interaction network was constructed, and hub genes were identified. The hub genes in patients were then validated by quantitative reverse transcription-PCR. Furthermore, hub gene-miRNA interactions were evaluated using the miRTarBase database. Finally, patient data on classical cardiovascular risk factors were collected, and plasma microRNA-146a (miR-146a) levels were detected. An individualized nomogram was constructed based on multivariate Cox regression analysis. Results A total of 239 DEGs were identified between the STEMI and control groups. Expression of S100A12 and miR-146a was significantly upregulated in STEMI samples compared with controls. STEMI patients with high levels of miR-146a had a higher risk of major adverse cardiovascular events (MACEs) than those with low levels of miR-146a (log-rank P = 0.034). Multivariate Cox regression analysis identified five statistically significant variables, including age, hypertension, diabetes mellitus, white blood cells, and miR-146a. A nomogram was constructed to estimate the likelihood of a MACE at one, two, and three years after STEMI. Conclusion The incidence of MACEs in STEMI patients expressing high levels of miR-146a was significantly greater than in those expressing low levels. MicroRNA-146a can serve as a biomarker for adverse prognosis of STEMI and might function in its pathogenesis by targeting S100A12, which may exert its role via an inflammatory response. In addition, our study presents a valid and practical model to assess the probability of MACEs within three years of STEMI.

Dataset Information

Circulating Cell and Plasma microRNA Profiles Differ between Non-ST-Segment and ST-Segment-Elevation Myocardial Infarction.

Publications

Circulating Cell and Plasma microRNA Profiles Differ between Non-ST-Segment and ST-Segment-Elevation Myocardial Infarction.

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