DNA microarray study of genes differentiating acute myocardial infarction patients from healthy persons

Głogowska-Ligus, Joanna; Dąbek, Józefa

doi:10.3109/1354750x.2012.668713

“…Differential gene expression patterns of leukocytes have previously been used successfully in the assessment of stable coronary disease 12 – 14 . Additionally, microarray-derived gene expression patterns in whole blood and PMBCs of patients presenting with AMI have been studied, and CEC-specific gene expression has been examined in patients with metastatic carcinoma and systemic sclerosis 15 – 21 . However, the prior studies in AMI were limited by their size and predictive ability.…”

Section: Introductionmentioning

confidence: 99%

A Whole Blood Molecular Signature for Acute Myocardial Infarction

Muse

¹

,

Kramer

²

,

Wang

³

et al. 2017

Sci Rep

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Chest pain is a leading reason patients seek medical evaluation. While assays to detect myocyte death are used to diagnose a heart attack (acute myocardial infarction, AMI), there is no biomarker to indicate an impending cardiac event. Transcriptional patterns present in circulating endothelial cells (CEC) may provide a window into the plaque rupture process and identify a proximal biomarker for AMI. Thus, we aimed to identify a transcriptomic signature of AMI present in whole blood, but derived from CECs. Candidate genes indicative of AMI were nominated from microarray of enriched CEC samples, and then verified for detectability and predictive potential via qPCR in whole blood. This signature was validated in an independent cohort. Our findings suggest that a whole blood CEC-derived molecular signature identifies patients with AMI and sets the framework to potentially identify the earlier stages of an impending cardiac event when used in concert with clinical history and other diagnostics where conventional biomarkers indicative of myonecrosis remain undetected.

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“…PBMCs from patients in the setting of AMI to identify the genes with greatest expression differences, but none have reported a similar discriminatory performance as the molecular signature reported here in whether from enriched CEC microarray or whole blood qPCR [15][16][17][18] .…”

Section: Likewise Several Other Groups Have Completed Gene Expressiomentioning

confidence: 74%

“…Differential gene expression patterns of leukocytes have previously been used successfully in the assessment of stable coronary disease [12][13][14] . Additionally, microarray-derived gene expression patterns in whole blood and PMBCs of patients presenting with AMI have been studied, and CEC-specific gene expression has been examined in patients with metastatic carcinoma and systemic sclerosis [15][16][17][18][19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

A Whole Blood Molecular Signature for Acute Myocardial Infarction

Muse

¹

,

Kramer

²

,

Wang

³

et al. 2016

Preprint

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Chest pain is a leading reason patients seek medical evaluation. While assays to detect myocyte death are used to diagnose a heart attack (acute myocardial infarction, AMI), there is no biomarker to indicate an impending cardiac event. Transcriptional patterns present in circulating endothelial cells (CEC) may provide a window into the plaque rupture process and identify a proximal biomarker for AMI. Thus, we aimed to identify a transcriptomic signature of AMI present in whole blood, but derived from CECs. Candidate genes indicative of AMI were nominated from microarray of enriched CEC samples, and then verified for detectability and predictive potential via qPCR in whole blood. This signature was validated in an independent cohort. Our findings suggest that a whole blood CEC-derived molecular signature identifies patients with AMI and sets the framework to potentially identify the earlier stages of an impending cardiac event when used in concert with clinical history and other diagnostics where conventional biomarkers indicative of myonecrosis remain undetected.Despite the significant reduction in the overall burden of cardiovascular disease (CVD) over the past decade, CVD still accounts for a third of all deaths in the United States and worldwide each year 1,2 . While efforts to identify and reduce risk factors for atherosclerotic heart disease (i.e. hypertension, dyslipidemia, diabetes mellitus, cigarette smoking, inactivity) remain the focus of primary prevention, the inability to accurately and temporally predict acute myocardial infarction (AMI) impairs our ability to further improve patient outcomes 3 . The current diagnostic evaluation for the presence of coronary artery disease relies on functional testing, which detects flow-limiting coronary stenosis, but it has been known for decades that most lesions underlying AMI are only of mild to moderate luminal narrowings prior to acute plaque rupture and not obstructing coronary blood flow 4-6 . Accordingly, there is an urgent need for improved diagnostics of the underlying arterial plaque dynamics, fissure and rupture 7,8 . Increased numbers of circulating endothelial cells (CEC) are known to be present not only in patients with AMI but also with unstable angina -marked by the absence of traditional biomarkers of myonecrosis (troponin, CK-MB) -and may provide a window into the pathophysiologic state preceding an acute atherothrombotic event and the development of myonecrosis 9,10 . The transition from stable atherosclerotic disease to a ruptured plaque with acute thrombo-occlusive disease is multifactorial and has been the subject of great study. It is thought to involve a combination of physical (sheer stress, thin fibrous cap vulnerability) and biochemical (proinflammatory, vasoactive) factors 4 . Prior to plaque rupture most atherosclerotic plaques responsible for acute coronary syndromes are not physiologically significant and there is no current diagnostic modality for accurate identification of unstable plaques 11 . Differential gene expression patter...

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“…To identify methylated proteins and putative Hmt1 substrates, the array data were filtered using S/Ns (details, see Materials and methods section). S/Ns have been used in DNA microarrays, RNA microarrays ( [21][22][23], reviewed in [24]), and peptide arrays ( [25], reviewed in [26]) and have proved useful with proteome arrays [27]. Through S/N-filtering and Measured signal intensity values of each protein spot were log2-transformed prior to Pearson correlation analysis between replicate protein spots.…”

Section: Hmt1 Treatment Of Arrays Identifies 42 Potential Substratesmentioning

confidence: 99%

Protein substrates of the arginine methyltransferase Hmt1 identified by proteome arrays

Low

¹

,

Im

²

,

Erce

³

et al. 2016

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Arginine methylation on nonhistone proteins is associated with a number of cellular processes including RNA splicing, protein localization, and the formation of protein complexes. In this manuscript, Saccharomyces cerevisiae proteome arrays carrying 4228 proteins were used with an antimethylarginine antibody to first identify 88 putatively arginine-methylated proteins. By treating the arrays with recombinant arginine methyltransferase Hmt1, 42 proteins were found to be possible substrates of this enzyme. Analysis of the putative arginine-methylated proteins revealed that they were predominantly nuclear or nucleolar in localization, consistent with the localization of Hmt1. Many are involved in known methylarginine-associated functions, such as RNA processing and ribonucleoprotein complex biogenesis, yet others are of newer classes, namely RNA/DNA helicases and tRNA-associated proteins. Using ex vivo methylation and MS/MS, a set of 12 proteins (Brr1, Dia4, Hts1, Mpp10, Mrd1, Nug1, Prp43, Rpa43, Rrp43, Spp381, Utp4, and Npl3), including the RNA helicase Prp43 and tRNA ligases Dia4 and Hts1, were all validated as Hmt1 substrates. Interestingly, the majority of these also had human orthologs, or family members, that have been documented elsewhere to carry arginine methylation. These results confirm arginine methylation as a widespread modification and Hmt1 as the major arginine methyltransferase in the S. cerevisiae cell.

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DNA microarray study of genes differentiating acute myocardial infarction patients from healthy persons

Abstract: The differentiating genes that we tracked down indicate possible linkage with atherosclerotis and could be a prognostic marker for development of cardiovascular diseases.

Cited by 6 publications

References 15 publications

A Whole Blood Molecular Signature for Acute Myocardial Infarction

A Whole Blood Molecular Signature for Acute Myocardial Infarction

A Whole Blood Molecular Signature for Acute Myocardial Infarction

Protein substrates of the arginine methyltransferase Hmt1 identified by proteome arrays

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