Circulating lncRNA ANRIL level positively correlates with disease risk, severity, inflammation level and poor prognosis of coronary artery disease (original) (raw)
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Plasma long non-coding RNA, CoroMarker, a novel biomarker for diagnosis of coronary artery disease
Clinical science (London, England : 1979), 2015
Long non-coding RNAs (lncRNAs) have been reported to be involved in the pathogenesis of cardiovascular disease (CVD), but whether circulating lncRNAs can serve as a coronary artery disease (CAD), biomarker is not known. The present study screened lncRNAs by microarray analysis in the plasma from CAD patients and control individuals and found that 265 lncRNAs were differentially expressed. To find specific lncRNAs as possible CAD biomarker candidates, we used the following criteria for 174 up-regulated lncRNAs: signal intensity ≥8, fold change >2.5 and P<0.005. According to these criteria, five intergenic lncRNAs were identified. After validation by quantitative PCR (qPCR), one lncRNA was excluded from the candidate list. The remaining four lncRNAs were independently validated in another population of 20 CAD patients and 20 control individuals. Receiver operating characteristic (ROC) curve analysis showed that lncRNA AC100865.1 (referred to as CoroMarker) was the best of these ...
Cardiovascular research, 2016
Long non-coding RNAs (lncRNAs) have been found to be involved in the pathogenesis of coronary artery disease (CAD). However, it remains to be established whether or not circulating lncRNAs can serve as biomarkers of CAD. Using a microarray-based lncRNA expression profiling, we found 86 lncRNAs that were differentially expressed in circulating peripheral blood monocytes (PBMCs) and plasma from 15 CAD patients and 15 control subjects. After choosing a consistent criterion (average normalized intensity ≥7 with significance <0.005), and confirmed by quantitative PCR (qPCR), only three lncRNAs (CoroMarker, BAT5, and IL21R-AS1) remained as candidate CAD biomarkers. Using the analysis of the area under the curve (AUC) of the receiver operating characteristic (ROC) in another pilot group and another larger cohort, CoroMarker was found to be the best candidate biomarker for CAD with an AUC of 0.920 and 95% confidence interval of 0.892-0.947. CoroMarker was independent from known CAD risk ...
International Journal of Molecular and Cellular Medicine, 2018
Animal cells possess thousands of long non-coding (lnc) RNAs, such as antisense noncoding RNA in the INK4 locus (ANRIL), which have regulatory roles in the cells’ molecular mechanisms, including X-chromosome inactivation, and developmental processes. These lnc RNAs are known to influence the extensive spectrum of age-related disorders. Accordingly, there is evidence for the role of these lnc RNAs in cardiovascular diseases, particularly coronary artery diseases (CAD). The aim of this study was to assess whether the expression of the lnc RNA ANRIL was associated with a susceptibility to CAD by evaluating the expression level of the two transcripts of ANRIL. Peripheral blood was taken from fifty patients affected by CAD and relative expression of ANRIL was determined by Real-Time PCR assay. The obtained data indicated that the EU741058 transcript expression level significantly decreased in CAD patients in comparison with the healthy individuals (P= 0.001). Furthermore, there was no si...
Differential Expression of Long Noncoding RNAs in Patients with Coronary Artery Disease
Molecular Syndromology, 2021
Tuberculosis (TB) remains a major worldwide health problem and has caused millions of deaths in the past few years. Current diagnostic methods, such as sputum smear microscopy and sputum culture, are time-consuming and cannot prevent the rapid spreading of TB during the diagnostic period. In this connection, detecting biomarkers specific to TB at molecular level in plasma of patients will provide a rapid means for diagnosis. In this study, we first evaluated the differential expression of the long non-coding RNAs (lncRNAs) in the plasma from patients with TB (TB positive), community acquired pneumonia (CAP) and healthy individuals (CG) using lncRNA microarray scanning. It was found that there were 2116 specific lncRNAs differentially expressed in the TB positive samples (1102 up-regulated and 1014 down-regulated), which accounted for 6.96% of total lncRNAs. Twelve differentially expressed lncRNAs discovered in microarray were subsequently validated by using real-time quantitative PCR (RT-qPCR). Two lncRNAs (ENST00000354432 and ENST00000427151) were further validated with more Tuberculosis samples. These results suggested the expression level of lncRNAs and the two validated lncRNAs in plasma could be the potential molecular biomarkers for the rapid diagnosis of Tuberculosis.
Association of Increased Levels of lncRNA H19 in PBMCs with Risk of Coronary Artery Disease Citation
Volume 20, Number 4, Jan-Mar(Winter) 2019, Serial Number: 80, 2019
Objective: Considerable research shows that long non-coding RNAs, those longer than 200 nucleotides, are involved in several human diseases such as various cancers and cardiovascular diseases. Their significant role in regulating the function of endothelial cells, smooth muscle cells, macrophages, vascular inflammation, and metabolism indicates the possible effects of lncRNAs on the progression of atherosclerosis which is the most common underlying pathological process responsible for coronary artery disease (CAD). The aim of present study was to assess whether the expression of the lnc RNA H19 was associated with a susceptibility to CAD by evaluating the expression level of H19 in the peripheral blood. Materials and Methods: A case-control study of 50 CAD patients and 50 age and sex-matched healthy controls was undertaken to investigate whether the H19 lncRNA expression level is associated with a CAD using Taqman Real-Time polymerase chain reaction (PCR). Results: The subsequent result indicated that the H19 lncRNA was over-expressed in CAD patients in comparison with the controls. However, it was not statistically significant. This overexpression may be involved in coronary artery disease progression. Conclusion: We report here, the up-regulation of H19 lncRNA in the whole blood of CAD patients and suggest a possible role for H19 in the atherosclerosis process and its consideration as novel biomarker for CAD.
Long non-coding RNAs in the atherosclerotic plaque
Atherosclerosis, 2017
Genetic and environmental factors are important components of the development of atherosclerosis. Long non-coding RNA (lncRNAs) have emerged as regulators of multiple pathophysiological pathways in the cardiovascular system. Here, we investigated potential associations between lncRNAs and atherosclerosis. Tissue samples from atherosclerotic coronary artery plaques and non-atherosclerotic internal mammary artery were obtained from 20 patients during coronary artery bypass surgery. Expression levels of five lncRNAs known to be associated with coronary artery disease were measured using quantitative PCR. Cyclin-dependent kinase inhibitor 2B antisense RNA 1 (ANRIL) and myocardial infarction-associated transcript (MIAT) were more expressed in the atherosclerotic arteries compared to the non-atherosclerotic arteries. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was less expressed in the atherosclerotic plaques. Expression levels of potassium voltage-gated channel, KQT-l...
Association of Increased Levels of lncRNA H19 in PBMCs with Risk of Coronary Artery Disease
Cell Journal (Yakhteh), 2019
Objective Considerable research shows that long non-coding RNAs, those longer than 200 nucleotides, are involved in several human diseases such as various cancers and cardiovascular diseases. Their significant role in regulating the function of endothelial cells, smooth muscle cells, macrophages, vascular inflammation, and metabolism indicates the possible effects of lncRNAs on the progression of atherosclerosis which is the most common underlying pathological process responsible for coronary artery disease (CAD). The aim of present study was to assess whether the expression of the lnc RNA H19 was associated with a susceptibility to CAD by evaluating the expression level of H19 in the peripheral blood. Materials and Methods A case-control study of 50 CAD patients and 50 age and sex-matched healthy controls was undertaken to investigate whether the H19 lncRNA expression level is associated with a CAD using Taqman Real-Time polymerase chain reaction (PCR). Results The subsequent resul...
The Roles of the Long Non-Coding RNA Transcripts in Cardiovascular Diseases
Bezmialem Science
For many years, proteins have been known be the major regulators in biological processes such as transcription and translation. However, in recent years, with the advent of high-throughput sequencing technology, a high-resolution map of the human transcriptome was made and a large number of non-protein coding RNA genes were discovered. Non-protein coding RNA genes (ncRNAs) are classified according to their size. Long non-coding RNAs (lncRNAs) are a group of ncRNAs that are >200 nucleotides long. LncRNAs are involved in many biological processes. Expression levels of and genetic variations in lncRNAs contribute to in vivo and in vitro pathophysiological processes and have been associated with many diseases. In recent years, numerous lncRNAs, which are associated with cardiovascular disease (CVD), have been identified. One of the major causes of CVD is atherosclerosis. The molecular processes involved in the formation and progression of atherosclerosis in vascular smooth muscle cells, endothelial cells, and monocytes/macrophages play an important role in the development of CVD. In the future, a better understanding of the biological functions of lncRNAs with their ever-increasing importance in the formation and development of atherosclerosis will shed light on the development of novel therapeutic approaches for CVD.
Identification of candidate long non-coding RNAs in response to myocardial infarction
BMC Genomics, 2014
Background: Long non-coding RNAs (lncRNAs) constitute a novel class of non-coding RNAs. LncRNAs regulate gene expression, thus having the possibility to modulate disease progression. In this study, we investigated the changes of lncRNAs expression in the heart after myocardial infarction (MI). Results: Adult male C57/BL6 mice were subjected to coronary ligation or sham operation. In a derivation group of 4 MI and 4 sham-operated mice sacrificed 24 hours after surgery, microarray analysis showed that MI was associated with up-regulation of 20 lncRNAs and down-regulation of 10 lncRNAs (fold-change >2). Among these, 2 lncRNAs, called myocardial infarction-associated transcript 1 (MIRT1) and 2 (MIRT2), showed robust up-regulation in the MI group: 5-fold and 13-fold, respectively. Up-regulation of these 2 lncRNAs after MI was confirmed by quantitative PCR in an independent validation group of 8 MI and 8 sham-operated mice (9-fold and 16-fold for MIRT1 and MIRT2, P < 0.001). In a time-course analysis involving 21 additional MI mice, the expression of both lncRNAs peaked 24 hours after MI and returned to baseline after 2 days. In situ hybridization revealed an up-regulation of MIRT1 expression in the left ventricle of MI mice. Expression of MIRT1 and MIRT2 correlated with the expression of multiple genes known to be involved in left ventricular remodeling. Mice with high level of expression of MIRT1 and MIRT2 had a preserved ejection fraction.
Genetics and Molecular Biology, 2019
Long non-coding RNAs (lncRNAs) are implicated in various cellular and pathological processes. Two lncRNAs, myocardial infarction-associated transcript (MIAT) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), may be involved in the pathogenesis of coronary artery disease (CAD). Here, we aimed to determine the relative circulating levels of MIAT and MALAT1 in 110 stable CAD patients and 117 controls and to correlate their levels with the clinical and laboratory data. Peripheral blood expression levels were quantified by Real-Time qPCR. The median MIAT expression level in CAD patients was significantly 12-fold higher than controls (p<0.001). Otherwise, the median MALAT1 expression level was comparable in patient and control groups. Both lncRNAs showed significantly higher relative expression levels in patients with positive history of previous cardiac ischemic events, and MIAT showed significantly higher expression in diabetic CAD patients. The area under the curve of MIAT (0.888 ± 0.02 with sensitivity 95.5% and specificity 72.7%), was significantly larger than that of MALAT1 (0.601 ± 0.04 with sensitivity 50% and specificity 63.6%) for detecting the presence of significant CAD. The current findings suggest that lncRNA MIAT could have a diagnostic significance in CAD patients. MALAT1 levels, however, are not sufficiently reliable to have much clinical use in our cases.