Circulating microRNA as a Biomarker for Coronary Artery Disease (original) (raw)

Circulating microRNAs strongly predict cardiovascular death in patients with coronary artery disease-results from the large AtheroGene study

European heart journal, 2016

Stratification for subsequent coronary events among patients with coronary artery disease (CAD) is of considerable interest because of the potential to guide secondary preventive therapies. Recently, we identified eight microRNAs (miRNAs), which facilitated acute coronary syndrome (ACS) diagnosis. In this study, we aimed to evaluate their potential role as prognostic biomarkers for cardiovascular disease. The serum concentrations of eight candidate miRNAs -miR-19a, miR-19b, miR-132, miR-140-3p, miR-142-5p, miR-150, miR-186, and miR-210 were measured in a cohort of 1112 patients with documented CAD-including 430 patients with ACS and 682 patients with stable angina pectoris. Cardiovascular death was the main outcome measure. During a median follow-up of 4.0 years, most miRNAs reliably predicted cardiovascular death in ACS patients. Cox regression analyses indicated that in particular miR-132 (HR 2.85 per 1 SD increase, P = 0.022), miR-140-3p (HR 2.88 per 1 SD increase, P = 0.022), an...

Circulating microRNAs as possible biomarkers for coronary artery disease: a narrative review

EJIFCC, 2019

Coronary artery disease is one of the most common cardiovascular diseases in the world. Involvement of microRNAs on the pathogenesis of this disease was reported either in beneficial or detrimental way. Different studies have also speculated that circulating microRNAs can be applied as promising biomarkers for the diagnosis of coronary artery disease. Particularly, microRNA-133a seems to fulfill the criteria of ideal biomarkers due to its role in the diagnosis, severity assessment and in prognosis. The panel of circulating microRNAs has also improved the predictive power of coronary artery disease compared to single microRNAs. In this review, the role of circulating microRNAs for early detection, severity assessment and prognosis of coronary artery disease were reviewed.

Circulating microRNA-378 levels serve as a novel biomarker for assessing the severity of coronary stenosis in patients with coronary artery disease

Bioscience Reports, 2019

Background: Circulating microRNAs (miRNA) are steady preserved in blood plasma. Multiple evidences have shown that miRNAs play a crucial role in cardiovascular disease including miRNA-378, which has been illustrated to participate in diverse physiological and pathological processes of cardiovascular disease. In the present study, we aim to explore the expression of plasma miRNA-378 and its clinical significance in patients with coronary artery disease (CAD). Methods: MiRNA-378 expression in blood plasma was performed by quantitative real-time PCR (qRT-PCR) in 215 CAD patients and 52 matched controls of healthy populations. Medical information of all patients including the results of coronary angiography (CAG) was acquired through hospital information system (HIS). Spearman’s correlation, binary linear regression, and covariance analysis were used to examine the association between miRNA-378 and relative clinical risk factors. Receiver operating characteristic curve analysis was appl...

Circulating Micrornas as Predictive Biomarker of Incident Myocardial Infarction

Journal of the American College of Cardiology, 2012

Background and aims: Several risk prediction models for coronary heart disease (CHD) are available today, however, they only explain a modest proportion of the incidence. Circulating microRNAs (miRs) have recently been associated with processes in CHD development, and may therefore represent new potential risk markers. The aim of the study was to assess the incremental value of adding circulating miRs to the Framingham Risk Score (FRS). Methods: This is a case-control study with a 10-year observation period, with fatal and non-fatal myocardial infarction (MI) as endpoint. At baseline, ten candidate miRs were quantified by real-time polymerase chain reaction in serum samples from 195 healthy participants (60-79 years old). During the follow-up, 96 participants experienced either a fatal (n = 36) or a non-fatal MI (n = 60), whereas the controls (n = 99) remained healthy. By using best subset logistic regression, we identified the miRs that together with the FRS for hard CHD best predicted future MI. The model evaluation was performed by 10-fold cross-validation reporting area under curve (AUC) from the receiver operating characteristic curve (ROC). Results: The best miR-based logistic regression risk-prediction model for MI consisted of a combination of miR-21-5p, miR-26a-5p, mir-29c-3p, miR-144-3p and miR-151a-5p. By adding these 5 miRs to the FRS, AUC increased from 0.66 to 0.80. In comparison, adding other important CHD risk factors (waist-hip ratio, triglycerides, glucose, creatinine) to the FRS only increased AUC from 0.66 to 0.68. Conclusions: Circulating levels of miRs can add value on top of traditional risk markers in predicting future MI in healthy individuals.

Vascular Tissue Specific miRNA Profiles Reveal Novel Correlations with Risk Factors in Coronary Artery Disease

Biomolecules, 2021

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Non-coding RNAs have already been linked to CVD development and progression. While microRNAs (miRs) have been well studied in blood samples, there is little data on tissue-specific miRs in cardiovascular relevant tissues and their relation to cardiovascular risk factors. Tissue-specific miRs derived from Arteria mammaria interna (IMA) from 192 coronary artery disease (CAD) patients undergoing coronary artery bypass grafting (CABG) were analyzed. The aims of the study were 1) to establish a reference atlas which can be utilized for identification of novel diagnostic biomarkers and potential therapeutic targets, and 2) to relate these miRs to cardiovascular risk factors. Overall, 393 individual miRs showed sufficient expression levels and passed quality control for further analysis. We identified 17 miRs–miR-10b-3p, miR-10-5p, miR-17-3p, miR-21-5p, miR-151a-5p, miR-181a-5p, miR-185-5p, miR-194-5p, ...

Association of Circulating microRNAs with Coronary Artery Disease and Usefulness for Reclassification of Healthy Individuals: The REGICOR Study

Journal of Clinical Medicine

Risk prediction tools cannot identify most individuals at high coronary artery disease (CAD) risk. Oxidized low-density lipoproteins (oxLDLs) and microRNAs are actively involved in atherosclerosis. Our aim was to examine the association of CAD and oxLDLs-induced microRNAs, and to assess the microRNAs predictive capacity of future CAD events. Human endothelial and vascular smooth muscle cells were treated with oxidized/native low-density lipoproteins, and microRNA expression was analyzed. Differentially expressed and CAD-related miRNAs were examined in serum samples from (1) a case-control study with 476 myocardial infarction (MI) patients and 487 controls, and (2) a case-cohort study with 105 incident CAD cases and 455 randomly-selected cohort participants. MicroRNA expression was analyzed with custom OpenArray plates, log rank tests and Cox regression models. Twenty-one microRNAs, two previously undescribed (hsa-miR-193b-5p and hsa-miR-1229-5p), were up- or down-regulated upon cell...

Circulating miRNAs as biomarkers in cardiovascular diseases

European review for medical and pharmacological sciences, 2019

Cardiovascular diseases (CVDs) have shown a high prevalence every year, presenting arterial hypertension as prime factor for their development, also driven by population growth, the aging of population and epidemiologic changes in disease. One of the main challenges in the study of CVD is the identification of reliable biomarkers that can be used in clinical practice and, in this context, microRNAs (miRNAs) have attracted much attention recently. MiRNAs are small non-coding RNAs, identified as post-transcriptional regulators of the expression of several genes both in physiologic and pathologic conditions. They have been studied as possible biomarkers, since they are highly expressed in the vascular system and are crucial modulators for the differentiation, contraction, migration and apoptosis of vascular cells, so modifications in their expression can cause several vascular alterations. Thus, this review aimed to compile the main studies regarding the role of miRNAs in the developme...

Utility of Circulating MicroRNAs as Clinical Biomarkers for Cardiovascular Diseases

BioMed Research International, 2015

MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene and protein expression by translational repression and/or mRNA degradation. miRNAs are implicated in the pathogenesis of various cardiovascular diseases and have become potential targets for therapeutic intervention. Their stability and presence in variety of readily accessible cell types including whole blood, serum, plasma, and other body fluids render them as potential source of a clinical biomarker. This review provides a brief overview of miRNA biogenesis and function, the diagnostic potential of circulating extracellular miRNA and their specific role in vivo in various cardiovascular settings, and their future perspective as clinical biomarkers. It is clearly evident from experimental studies that miRNAs are responsible for the regulation of several biological functions and alterations in cardiovascular diseases. Current data supports the concept of using circulating miRNAs as a biomarker in cardiovascular...

The distribution of circulating microRNA and their relation to coronary disease

F1000Research, 2012

are small RNAs that regulate gene Background: expression by suppressing protein translation and may influence RNA expression. MicroRNAs are detected in extracellular locations such as plasma; however, the extent of miRNA expression in plasma its relation to cardiovascular disease is not clear and many clinical studies have utilized array-based platforms with poor reproducibility. Initially, to define distribution of miRNA in human Methods and Results: blood; whole blood, platelets, mononuclear cells, plasma, and serum from 5 normal individuals were screened for 852 miRNAs using high-throughput micro-fluidic quantitative RT-PCR (qRT-PCR). In total; 609, 448, 658, 147, and 178 miRNAs were found to be expressed in moderate to high levels in whole blood, platelets, mononuclear cells, plasma, and serum, respectively, with some miRNAs uniquely expressed. To determine the cardiovascular relevance of blood miRNA expression, plasma miRNA (n=852) levels were measured in 83 patients presenting for cardiac catheterization. Eight plasma miRNAs were found to have over 2-fold increased expression in patients with significant coronary disease (≥70% stenosis) as compared to those with minimal coronary disease (less than 70% stenosis) or normal coronary arteries. Expression of miR-494, miR-490-3p, and miR-769-3p were found to have significantly different levels of expression. Using a multivariable regression model including cardiovascular risk factors and medications, hsa-miR-769-3p was found to be significantly correlated with the presence of significant coronary atherosclerosis. This study utilized a superior high-throughput qRT-PCR based Conclusions: method and found that miRNAs are found to be widely expressed in human Referees