Dataset Information

Association between Exosomal miRNAs and Coronary Artery Disease by Next-Generation Sequencing.

ABSTRACT: Among various bio-informative molecules transferred by exosomes between cells, micro RNAs (miRNAs), which remain remarkably stable even after freeze-and-thaw cycles, are excellent candidates for potential biomarkers for coronary artery disease (CAD). Blood samples were collected from the coronary arteries of 214 patients diagnosed with three-vessel CAD and 140 without CAD. After precipitation extraction, the amounts of exosomes were found to decrease with increased age and three-vessel CAD. Next-generation sequencing was performed to further explore the possible relationship between exosomal miRNAs and CAD. Eight exosomal miRNAs showed altered expression associated with CAD. The up-regulated miRNAs in CAD were miRNA-382-3p, miRNA-432-5p, miRNA-200a-3p, and miRNA-3613-3p. The down-regulated miRNAs were miRNA-125a-5p, miRNA-185-5p, miRNA-151a-3p, and miRNA-328-3p. We successfully demonstrated particular exosomal miRNAs that may serve as future biomarkers for CAD.

SUBMITTER: Chang SN

PROVIDER: S-EPMC8750494 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Association between Exosomal miRNAs and Coronary Artery Disease by Next-Generation Sequencing.

Chang Sheng-Nan SN Chen Jien-Jiun JJ Wu Jo-Hsuan JH Chung Yao-Te YT Chen Jin-Wun JW Chiu Chu-Hsuan CH Liu Chia-Ju CJ Liu Meng-Tsun MT Chang Yi-Cheng YC Li Chin C Lin Jou-Wei JW Hwang Juey-Jen JJ Lien Wen-Pin WP

Cells 20211229 1

<h4>Background</h4>Among various bio-informative molecules transferred by exosomes between cells, micro RNAs (miRNAs), which remain remarkably stable even after freeze-and-thaw cycles, are excellent candidates for potential biomarkers for coronary artery disease (CAD).<h4>Methods</h4>Blood samples were collected from the coronary arteries of 214 patients diagnosed with three-vessel CAD and 140 without CAD. After precipitation extraction, the amounts of exosomes were found to decrease with increa ...[more]

PMID: 35011660

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Project description:Exosomal miRNAs are currently being explored as a novel class of biomarkers in cardiovascular diseases. However, few reports have focused on the value of circulating exosomal miRNAs as biomarkers for stable coronary artery disease (SCAD). Here, we aimed to investigate whether miRNAs involved in cardiovascular diseases in circulating exosomes could serve as novel diagnostic biomarkers for SCAD. Firstly, the serum exosomes were isolated and purified by the ExoQuick reagent and identified by transmission electron microscopy, western blot, and nanoparticle tracking analysis. Then, the purified exosomes were quantified by measuring the exosome protein concentration and calculating the total protein amount. Next, eight miRNAs involved in cardiovascular diseases, miR-192-5p, miR-148b-3p, miR-125a-3p, miR-942-5p, miR-149-5p, miR-32-5p, miR-144-3p, and miR-142-5p, were quantified in circulating exosomes from the control group (n = 20) and the SCAD group (n = 20) by quantitative real-time polymerase chain reaction (qPCR). Finally, the gene targets of the differentially expressed miRNAs were predicted, and the functions and signaling pathways of these targets were analyzed using an online database. The isolated exosomes had a bilayer membrane with a diameter of about 100 nm and expressed exosomal markers including CD63, Tsg101, and Flotillin but negatively expressed Calnexin. Both the exosome protein concentration and total protein amount exhibited no significant differences between the two groups. The qPCR assay demonstrated that among the eight miRNAs, the expression levels of miR-942-5p, miR-149-5p, and miR-32-5p in the serum exosomes from the SCAD group were significantly higher than that from the control group. And the three miRNAs for SCAD diagnosis exhibited AUC values of 0.693, 0.702, and 0.691, respectively. GO categories and signaling pathways analysis showed that some of the predictive targets of these miRNAs were involved in the pathophysiology processes of SCAD. In conclusion, our findings suggest that serum exosomal miR-942-5p, miR-149-5p, and miR-32-5p may serve as potential diagnostic biomarkers for SCAD.

Project description:Background and aimsVariation in micro-RNA (miRNA) levels in blood has been associated with alterations of physiological functions of the cardiovascular system. Circulating miRNA have the potential to become reliable biomarkers for risk stratification and early detection of cardiovascular events. Recurrent thrombotic events in patients with established coronary artery disease (CAD) demonstrate the need for personalized approaches to secondary prevention, especially in light of recent novel treatment approaches.MethodsIn a single center cohort study, whole blood samples were collected from 437 subjects undergoing cardiac catheterization, who were followed for recurrent cardiovascular events during a mean follow up of 1.5 years. We selected a case cohort (n = 22) with recurrent thrombotic events on standard medical therapy (stent thrombosis (n = 6) or spontaneous myocardial infarction (MI) (n = 16)) and a matched cohort with CAD, but uneventful clinical follow up (n = 26), as well as a control group with cardiovascular risk factors, but without angiographic CAD (n = 24). We performed complete miRNA next generation sequencing of RNA extracted from whole blood samples (including leukocytes and platelets).ResultsA differential pattern of miRNA expression was found among controls, CAD patients with no events, and CAD patients with recurrent events. MiRNA previously associated with MI, CAD, endothelial function, vascular smooth muscle cells, platelets, angiogenesis, heart failure, cardiac hypertrophy, arrhythmia, and stroke were found variably expressed in our case-control cohorts. Seventy miRNA (FDR <0.05) were linked to the risk of recurrent myocardial infarction and future stent thrombosis, as compared to CAD patients with subsequently uneventful follow up.ConclusionsMiRNA next generation sequencing demonstrates altered fingerprint profile of whole blood miRNA expression among subjects with subsequent recurrent thrombotic events on standard medical therapy ('non-responders'), as compared to subjects with no recurrent cardiovascular events. MiRNA profiling may be useful to identify high risk subjects and provide additional insights into disease mechanisms not currently attenuated with standard medical therapy used in CAD treatment.

Project description:BackgroundCoronary artery stenosis induces heart diseases including acute coronary syndrome (ACS). Some studies reported the ceramide species are associated with the ACS and major adverse cardia and cerebrovascular events (MACE). However, few studies investigated the association between plasma ceramide levels and the severity of stenosis, together with the onset of diseases. This aim of the present study was to investigate the association betweencertain ceramide species, coronary artery stenosis and acute coronary syndrome.MethodsFive hundred fifty-three patients with definite or suspected CAD were recruited and received angiography. Subjects were assigned into 4 groups according to the severity of coronary artery stenosis. The measurements of 4 plasma ceramide species, namely, Cer (d18:1/16:0), Cer (d18:1/18:0), Cer (d18:1/24:1), Cer (d18:1/24:0) were carried out by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the ratio of Cer (d18:1/16:0), Cer (d18:1/18:0) and Cer (d18:1/24:1) to Cer (18:1/24:0), respectively, were calculated as index to evaluate the association between plasma ceramides levels and coronary artery stenosis. Multiple logistic regression analysis was used to establish the prognostic model for the prediction of ACS risk.ResultsAfter the adjustment by multiple clinical risk factors including age, gender, pre-existing myocardial/cerebral infarction, hemoglobin A1c% (HbA1c%), smoking and the diagnosis during index hospitalization, multiple logistic regression analysis showed that the high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c%, unstable angina (UAP) and acute myocardial infarction (AMI) diagnosis (compared with atherosclerosis) during index hospitalization were associated with more severe coronary artery stenosis. Furthermore, the prognostic model was established after adjustment of risk factors and the area under curve (AUC) of receiver operating characteristics (ROC) for the prognostic model was 0.732 and 95% CI was 0.642-0.822.ConclusionThe severity of coronary artery stenosis is associated with high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c% and AMI. Although the reported prognostic model showed a good discrimination, further investigation on long term MACE is needed to evaluate the role of ceramide for the prediction of MACE risk.

Project description:Large-scale genome-wide association studies have identified hundreds of single-nucleotide variants (SNVs) significantly associated with coronary artery disease (CAD). However, collectively, these explain <20% of the heritability. Hypothesis: Here, we hypothesize that mitochondrial (MT)-SNVs might present one potential source of this “missing heritability”. Methods: We analyzed 265 MT-SNVs in ~500,000 UK Biobank individuals, exploring two different CAD definitions: a more stringent (myocardial infarction and/or revascularization; HARD = 20,405), and a more inclusive (angina and chronic ischemic heart disease; SOFT = 34,782). Results: In HARD cases, the most significant (p < 0.05) associations were for m.295C>T (control region) and m.12612A>G (ND5), found more frequently in cases (OR = 1.05), potentially related to reduced cardiorespiratory fitness in response to exercise, as well as for m.12372G>A (ND5) and m.11467A>G (ND4), present more frequently in controls (OR = 0.97), previously associated with lower ROS production rate. In SOFT cases, four MT-SNVs survived multiple testing corrections (at FDR < 5%), all potentially conferring increased CAD risk. Of those, m.11251A>G (ND4) and m.15452C>A (CYB) have previously shown significant associations with body height. In line with this, we observed that CAD cases were slightly less physically active, and their average body height was ~2.00 cm lower compared to controls; both traits are known to be related to increased CAD risk. Gene-based tests identified CO2 associated with HARD/SOFT CAD, whereas ND3 and CYB associated with SOFT cases (p < 0.05), dysfunction of which has been related to MT oxidative stress, obesity/T2D (CO2), BMI (ND3), and angina/exercise intolerance (CYB). Finally, we observed that macro-haplogroup I was significantly (p < 0.05) more frequent in HARD cases vs. controls (3.35% vs. 3.08%), potentially associated with response to exercise. Conclusions: We found only spurious associations between MT genome variation and HARD/SOFT CAD and conclude that more MT-SNV data in even larger study cohorts may be needed to conclusively determine the role of MT DNA in CAD.

Dataset Information

Association between Exosomal miRNAs and Coronary Artery Disease by Next-Generation Sequencing.

Publications

Association between Exosomal miRNAs and Coronary Artery Disease by Next-Generation Sequencing.

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