Novel genes detected by transcriptional profiling from whole-blood cells in patients with early onset of acute coronary syndrome

Silbiger, Vivian N.; Luchessi, André Ducati; Hirata, Rosário Dominguez Crespo; Lima-Neto, Lidio Gonçalves; Cavichioli, Débora; Carracedo, Ángel; Brión, Marı́a; Dopazo, Joaquı́n; García‐García, Francisco; Santos, Elizabete Silva dos; Ramos, Rui Fernando; Sampaio, Marcelo Ferraz; Armaganijan, Dikran; Sousa, Amanda G. M. R.; Hirata, Mário Hiroyuki

doi:10.1016/j.cca.2013.03.011

Cited by 49 publications

(47 citation statements)

References 27 publications

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“…Statistically, these differences are suggestive and do not pass a strict Bonferroni correction for multiple testing. However, we do provide support for the increased expression of KCNE1 (p=0.00793) and ECHDC3 (p=0.0141) as well as decreased expression of MIAT (p=0.0449) in STEMI platelets compared to NSTEMI, as previously reported in whole blood, as well as increased expression of FKBP5 (p=0.000694) in platelets from STEMI patients (Table IIIb, Table IV) [21-23]. Our observation of increased MYL4 expression in NSTEMI compared to STEMI platelets is in the opposite direction as previously reported [21].…”

Section: Resultssupporting

confidence: 87%

“…However, we do provide support for the increased expression of KCNE1 (p=0.00793) and ECHDC3 (p=0.0141) as well as decreased expression of MIAT (p=0.0449) in STEMI platelets compared to NSTEMI, as previously reported in whole blood, as well as increased expression of FKBP5 (p=0.000694) in platelets from STEMI patients (Table IIIb, Table IV) [21-23]. Our observation of increased MYL4 expression in NSTEMI compared to STEMI platelets is in the opposite direction as previously reported [21]. Pathway analyses of suggestively differentially expressed genes (p≤0.05) showed enrichment for metabolic and mitochondrial-related pathways, including the synthesis of metabolic enzymes (panthothenate and CoA) and metabolism of nucleotide sugars, amino acids, and glycerophospholipids (Supplemental Tables 14-17).…”

Section: Resultssupporting

confidence: 87%

“…However, little is known regarding the roles platelets may play in differences between STEMI and NSTEMI subtypes. Previous studies examining expression differences between STEMI and NSTEMI cases in whole blood showed that ECHDC3 and KCNE1 are differentially higher expressed and MIAT lower expressed, respectively [21,22]. We provide support for these expression differences with the same direction of effect in platelets.…”

Section: Discussionsupporting

confidence: 72%

“…These differences in platelet reactivity and disease progression may result from gene expression differences between STEMI and NSTEMI cases. Previous studies in whole blood identified several differentially expressed transcripts between STEMI and NSTEMI cases including KCNE1 , ECHDC3 , and MIAT [21,22]. Another study identified 54 differentially expressed transcripts in platelets between STEMI and stable coronary artery disease (CAD) patients, with CD69 and S100A9 being the strongest candidates [23].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction

et al. 2015

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Transcripts in platelets are largely produced in precursor megakaryocytes but remain physiologically-active as platelets translate RNAs and regulate protein/RNA levels. Recent studies using transcriptome sequencing (RNA-seq) characterized the platelet transcriptome in limited numbers of non-diseased individuals. Here, we expand upon these RNA-seq studies by completing RNA-seq in platelets from 32 patients with acute myocardial infarction (MI). Our goals were to characterize the platelet transcriptome using a population of patients with acute MI and relate gene expression to platelet aggregation measures and ST-segment elevation MI (STEMI) (n=16) versus non-STEMI (NSTEMI) (n=16) subtypes. Similar to other studies, we detected 9,565 expressed transcripts, including several known platelet-enriched markers (e.g., PPBP, OST4). Our RNA-seq data strongly correlated with independently ascertained platelet expression data and showed enrichment for platelet-related pathways (e.g., wound response, hemostasis, and platelet activation), as well as actin-related and post-transcriptional processes. Several transcripts displayed suggestively higher (FBXL4, ECHDC3, KCNE1, TAOK2, AURKB, ERG, and FKBP5) and lower (MIAT, PVRL3and PZP) expression in STEMI platelets compared to NSTEMI. We also identified transcripts correlated with platelet aggregation to TRAP (ATP6V1G2, SLC2A3), collagen (CEACAM1, ITGA2), and ADP (PDGFB, PDGFC, ST3GAL6). Our study adds to current platelet gene expression resources by providing transcriptome-wide analyses in platelets isolated from patients with acute MI. In concert with prior studies, we identify various genes for further study in regards to platelet function and acute MI. Future platelet RNA-seq studies examining more diverse sets of healthy and diseased samples will add to our understanding of platelet thrombotic and non-thrombotic functions.

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Section: Resultssupporting

confidence: 87%

Section: Resultssupporting

confidence: 87%

Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction

et al. 2015

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“…In a microarray-based gene expression study performed previously by our research team, we found that ECHDC3 mRNA expression was significantly increased within 2 h after an acute coronary syndrome, suggesting this gene could be a potential novel biomarker for the early stage of an acute episode [3]. However, the function of ECHDC3 or its involvement with cardiovascular diseases is scarcely explored in the literature, which might be due to its recent identification.…”

Section: Introductionmentioning

confidence: 99%

The relationship of the oleic acid level and ECHDC3 mRNA expression with the extent of coronary lesion

et al. 2016

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GC–MS validation and analysis of targeted plasma metabolites related to carbonyl stress in type 2 diabetes mellitus patients with and without acute coronary syndrome

Bora,

Adole,

Vinod

et al. 2024

Biomedical Chromatography

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Methylglyoxal (MG) is responsible for advanced glycation end‐product formation, the mechanisms leading to diabetes pathogenesis and complications like acute coronary syndrome (ACS). Sugar metabolites, amino acids and fatty acids are possible substrates for MG. The study aimed to measure plasma MG substrate levels using a validated gas chromatography–mass spectrometry (GC–MS) method and explore their association with ACS risk in type 2 diabetes mellitus (T2DM). The study included 150 T2DM patients with ACS as cases and 150 T2DM without ACS as controls for the analysis of glucose, fructose, ribulose, sorbitol, glycerol, pyruvate, lactate, glycine, serine, threonine, C16:0, C16:1, C18:0, C18:1, C18:2, C18:3, C20:0 and C22:6 by GC–MS. Validated GC–MS methods were accurate, precise and sensitive. Cases significantly differed in plasma MG and metabolite levels except for lactate, C16:0, C18:0, C18:2, and C18:3 levels compared with controls. On multivariable logistic regression, plasma C20:0, C18:1, glycine and glycerol levels had increased odds of ACS risk. On multivariate receiver operating characteristic analysis, a model containing plasma C20:0, C16:1, C18:1, C18:2, serine, glycerol, lactate and threonine levels had the highest area under the curve value (0.932) for ACS diagnosis. In conclusion, plasma C20:0, C16:1, C18:1, glycine, glycerol and sorbitol levels were associated with ACS risk in T2DM.

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Novel genes detected by transcriptional profiling from whole-blood cells in patients with early onset of acute coronary syndrome

Abstract: Transcriptomic analysis by microarray technology demonstrated differential expression during a 48 h time course suggesting a potential use of some of these genes as biomarkers for very early stages of ACS, as well as for monitoring early cardiac ischemic recovery.

Cited by 49 publications

References 27 publications

Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction

Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction

The relationship of the oleic acid level and ECHDC3 mRNA expression with the extent of coronary lesion

GC–MS validation and analysis of targeted plasma metabolites related to carbonyl stress in type 2 diabetes mellitus patients with and without acute coronary syndrome

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