Identification of a circulating microRNAs biomarker panel for non-invasive diagnosis of coronary artery disease: case–control study

Abdallah, Hoda Y.; Hassan, Ranya; Fareed, Ahmed; Abdelgawad, Mai; Mostafa, Sally Abdallah; Mohammed, Eman A.

doi:10.1186/s12872-022-02711-9

Cited by 14 publications

(12 citation statements)

References 108 publications

(83 reference statements)

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“…miR-133a-3p affects the progression of atherosclerosis ( Libby et al, 2019 ), cardiac remodeling ( Li et al, 2018 ), myocardial infarction ( Paiva and Agbulut, 2017 ), ischemia-reperfusion injury ( Ye et al, 2011 ). Several studies have demonstrated that miR-133a-3p, which is considered as a candidate marker, is markedly downregulated in obesity and cardiovascular disease ( Kim et al, 2020 ; Abdallah et al, 2022 ). However, the specific role and mechanism of miR-133a-3p in atherosclerosis remains unclear.…”

Section: Discussionmentioning

confidence: 99%

miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injury

Xue,

Tong,

Zhang

et al. 2024

Front. Pharmacol.

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Background: Vascular endothelial injury is a contributing factor to the development of atherosclerosis and the resulting cardiovascular diseases. One particular factor involved in endothelial cell apoptosis and atherosclerosis is palmitic acid (PA), which is a long-chain saturated fatty acid. In addition, transient receptor potential melastatin 4 (TRPM4), a non-selective cation channel, plays a significant role in endothelial dysfunction caused by various factors related to cardiovascular diseases. Despite this, the specific role and mechanisms of TRPM4 in atherosclerosis have not been fully understood.Methods: The protein and mRNA expressions of TRPM4, apoptosis - and inflammation-related factors were measured after PA treatment. The effect of TRPM4 knockout on the protein and mRNA expression of apoptosis and inflammation-related factors was detected. The changes of intracellular Ca2+, mitochondrial membrane potential, and reactive oxygen species were detected by Fluo-4 AM, JC-1, and DCFH-DA probes, respectively. To confirm the binding of miR-133a-3p to TRPM4, a dual luciferase reporter gene assay was conducted. Finally, the effects of miR-133a-3p and TRPM4 on intracellular Ca2+, mitochondrial membrane potential, and reactive oxygen species were examined.Results: Following PA treatment, the expression of TRPM4 increases, leading to calcium overload in endothelial cells. This calcium influx causes the assemblage of Bcl-2, resulting in the opening of mitochondrial calcium channels and mitochondrial damage, ultimately triggering apoptosis. Throughout this process, the mRNA and protein levels of IL-1β, ICAM-1, and VCAM1 significantly increase. Database screenings and luciferase assays have shown that miR-133a-3p preferentially binds to the 3′UTR region of TRPM4 mRNA, suppressing TRPM4 expression. During PA-induced endothelial injury, miR-133a-3p is significantly decreased, but overexpression of miR-133a-3p can attenuate the progression of endothelial injury. On the other hand, overexpression of TRPM4 counteracts the aforementioned changes.Conclusion: TRPM4 participates in vascular endothelial injury caused by PA. Therefore, targeting TRPM4 or miR-133a-3p may offer a novel pharmacological approach to preventing endothelial injury.

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Section: Discussionmentioning

confidence: 99%

miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injury

Xue,

Tong,

Zhang

et al. 2024

Front. Pharmacol.

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“…Numerous studies have reported the relationship between miRNA146a rs2910164 polymorphism and different diseases such as auto‐immune, cancer, and CVDs. [ 17 ] miR‐146a is implicated in both inflammation and lipid homeostasis, [ 18,19 ] and functions by its inhibitory effect on oxidized low‐density lipoproteins and inflammatory response, [ 19 ] thus affecting the pathogenesis of atherosclerosis. [ 20 ]…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have reported the relationship between miRNA146a rs2910164 polymorphism and different diseases such as autoimmune, cancer, and CVDs. [17] miR-146a is implicated in both inflammation and lipid homeostasis, [18,19] and functions by its inhibitory effect on oxidized low-density lipoproteins and inflammatory response, [19] thus affecting the pathogenesis of atherosclerosis. [20] miR-4513 is a latterly identified miRNA, whose polymorphisms in the seed sequence are frequently combined with fasting glucose, LDL-cholesterol and total cholesterol, systolic and diastolic blood pressure, and human diseases such as CHD and lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Study the association of microRNA polymorphisms (miR‐146a, miR‐4513) with the risk of coronary heart diseases in Egyptian population

Ali

Radwan

Elaraby

et al. 2022

J Biochem & Molecular Tox

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Coronary heart disease (CHD) is the most prevalent cause of cardiovascular mortality in the world. It is well established that microRNAs (miRNAs) and their variants have an essential role in regulating the development of cardiovascular physiology, thus impacting the pathophysiology of heart diseases. This study was designed to determine the possible association of miRNA polymorphisms (miRNA-146a rs2910164C/G and miR-4513 rs2168518G/A) with susceptibility to CHD in Egyptian patients and their correlation with different biochemical parameters. The study comprised 300 participants, including 200 unrelated patients with CHD and 100 healthy controls. Anthropometric and blood biochemical parameters were measured as well genetic analysis for rs2910164C/G and rs2168518G/A polymorphisms were performed for all subjects using TaqMan real-time PCR assay. Our results revealed that the biomedical parameters have a significant correlation between CHD patients and healthy controls with a p < 0.05. Analyses of genotype distribution for (rs2910164 and rs2168518) revealed a significant association with CHD [odd ratio = 4.54, confidence interval (CI 95%) = (2.41-8.53)] and [odd ratio = 0.88, (CI 95%) = (0.83-0.92)], respectively. Furthermore, a statistically significant difference was detected between lipid profile levels and both rs2910164 and rs2168518 polymorphisms. The present study's findings indicated that the selected polymorphisms, miR-146a rs2910164 and miR-4513 rs2168518 could represent a useful biomarker for susceptibility to CHD in the Egyptian population. These genetic characteristics and personal habits and environmental factors may contribute to the development of CHD.

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“…Recent studies have unveiled the potentially important function of miRNA-126-5p in vascular diseases, including atherosclerosis, coronary artery disease, stroke, and diabetic vasculopathy. The action of miRNA-126-5p reflects its function in angiogenesis and inflammation [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Introducing Circulating Vasculature-Related Transcripts as Biomarkers in Coronary Artery Disease

et al. 2022

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Background Atherosclerotic plaque is considered the hallmark of atherosclerotic lesions in coronary atherosclerosis (CAS), the primary pathogenesis in coronary artery disease (CAD), which develops and progresses through a complex interplay between immune cells, vascular cells, and endothelial shear stresses. Early diagnosis of CAS is critical for avoiding plaque rupture and sudden death. Therefore, identifying new CAD biomarkers linked to vessel wall functions, such as RNA molecules with their distinct signature, is a promising development for these patients. With this rationale, the present study investigated the expression level of the vascular-related RNA transcripts (lncRNA ANRIL, miRNA-126-5p, CDK4, CDK6, TGF-β, E-cadherin, and TNF-α) implicated in the cellular vascular function, proliferation, and inflammatory processes. Methods A case-control study design with a total of 180 subjects classified participants into two groups; CAD and control groups. The relative expression levels of the seven transcripts under study-selected using online bioinformatics tools and current literature-were assessed in the plasma of all study participants using RT-qPCR. Their predictive significance testing, scoring of disease prioritization, enrichment analysis, and the miRNA-mRNA regulatory network was investigated. ResultsThe relative expression levels of all seven of the circulating vascular-related transcripts under study were statistically significant between CAD patients and controls. Receiver operating characteristic (ROC) analysis results indicated the statistical significance of all the transcripts under study with CDK4 showing the highest area under the curve (AUC) equivalent to 0.91, followed by E-cadherin (0.90), miRNA-126-5p (0.83), ANRIL (0.82), TNF-α (0.63), TGF-β (0.62), and CDK6 (0.59), in descending order. A strong association was detected between most of the transcripts studied in CAD patients with a significant Spearman's correlation coefficient with a two-tailed significance of p < 0.001. Network analysis revealed a strong relationship between the five circulating vasculature transcripts studied and their target miRNAs and miR-126-5p, but not for ANRIL. Conclusion The seven circulating vascular-related RNA transcripts under study could serve as potential CAD biomarkers, reflecting the cellular vascular function, proliferation, and inflammatory processes in CAD patients. Therefore, blood transcriptome analysis opens new frontiers for the non-invasive diagnosis of CAD.

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Identification of a circulating microRNAs biomarker panel for non-invasive diagnosis of coronary artery disease: case–control study

Cited by 14 publications

References 108 publications

miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injury

miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injury

Study the association of microRNA polymorphisms (miR‐146a, miR‐4513) with the risk of coronary heart diseases in Egyptian population

Introducing Circulating Vasculature-Related Transcripts as Biomarkers in Coronary Artery Disease

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