Circulating microRNAs identify patients at increased risk of in-stent restenosis after peripheral angioplasty with stent implantation

Stojković, Stefan; Jurisic, Miro; Kopp, Christoph W.; Koppensteiner, Renate; Huber, Kurt; Wojta, Johann; Gremmel, Thomas

doi:10.1016/j.atherosclerosis.2018.01.020

Cited by 35 publications

(31 citation statements)

References 60 publications

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“…The diagnostic potential of miR-21 for in-stent restenosis was also reported in a previous study (80). Elevated peripheral miR-92 and miR-195 levels were found to be good independent predictors for two years of target vessel revascularization (83). Similar to this finding, increased transcoronary expression of miR-133a had both diagnostic and prognostic significance for target vessel revascularization (84).…”

Section: Mirna and Restenosissupporting

confidence: 79%

MicroRNA and Cardiovascular Diseases

2020

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Cardiovascular diseases are one of the most common causes of death in both developing and developed countries worldwide. Even though there have been improvements in primary prevention, the prevalence of cardiovascular diseases continues to increase in recent years. Hence, it is crucial to both investigate the molecular pathophysiology of cardiovascular diseases in-depth and find novel biomarkers regarding the early and proper prevention and diagnosis of these diseases. MicroRNAs, or miRNAs, are endogenous, conserved, single-stranded non-coding RNAs of 21-25 nucleotides in length. miRNAs have important roles in various cellular events such as embryogenesis, proliferation, vasculogenesis, apoptosis, cell growth, differentiation, and tumorigenesis. They also have potential roles in the cardiovascular system, including angiogenesis, cardiac cell contractility, control of lipid metabolism, plaque formation, the arrangement of cardiac rhythm, and cardiac cell growth. Circulating miRNAs are promising novel biomarkers for purposes of the diagnosis and prognosis of cardiovascular diseases. Cell or tissue specificity, stability in serum or plasma, resistance to degradative factors such as freeze-thaw cycles or enzymes in the blood, and fast-release kinetics, provide the potential for miRNAs to be surrogate markers for the early and accurate diagnosis of disease and for predicting middle-or longterm prognosis. Moreover, it may be a logical approach to combine miRNAs with traditional biomarkers to improve risk stratification and long-term prognosis. In addition to their efficacy in both diagnosis and prognosis, miRNA-based therapeutics may be beneficial for treating cardiovascular diseases using novel platforms and computational tools and in combination with traditional methods of analysis. microRNAs are promising, novel therapeutic agents, which can affect multiple genes using different signaling pathways. miRNAs therapeutic modulation techniques have been used in the settings of atherosclerosis, acute myocardial infarction, restenosis, vascular remodeling, arrhythmias, hypertrophy and fibrosis, angiogenesis and cardiogenesis, aortic aneurysm, pulmonary hypertension, and ischemic injury. This review presents detailed information about miRNAs regarding structure and biogenesis, stages of synthesis and functions, expression profiles in serum/plasma of living organisms, diagnostic and prognostic potential as novel biomarkers, and therapeutic applications in various diseases.

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Section: Mirna and Restenosissupporting

confidence: 79%

MicroRNA and Cardiovascular Diseases

2020

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“…Blood was drawn from an antecubital vein during an outpatient visit 2-4 hours after intake of morning medication and was processed within 15 minutes to avoid swelling of platelets in EDTA blood. 16,17 MEA was determined by the Multiplate analyzer (Roche Diagnostics), as previously described. Isolation of ribonucleotide acid and the reverse transcription of miRNA was carried out as previously described.…”

Section: Blood Collection and Processingmentioning

confidence: 99%

“…Isolation of ribonucleotide acid and the reverse transcription of miRNA was carried out as previously described. 16,17 Briefly, total RNA including small RNAs was extracted from 200 μL of plasma using the miRNeasy Serum/Plasma Kit (Qiagen) and QIAcube (Qiagen) robotic workstation for semi-automated RNA purification following manufacturer's instructions. Synthetic Caenorhabditis elegans miR-39 (cel-miR-39, Qiagen) was spiked in each sample to normalize for extraction variation between samples.…”

Section: Blood Collection and Processingmentioning

confidence: 99%

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Course of platelet miRNAs after cessation of P2Y12 antagonists

Jäger

Stojković

Haller

et al. 2019

Eur J Clin Investigation

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Background: Circulating platelet micro-RNAs (miRNAs) may be used to monitor platelet function during dual antiplatelet therapy (DAPT). Aim of the study was to measure plasma levels of specific miRNAs (miRNA-223, -150, -21 and -126) after physician-driven cessation of chronic P2Y12 inhibition and to study differences in the expression levels of these miRNAs between the different oral P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor, respectively. Design: Patients with coronary artery disease (CAD) on DAPT maintenance dose (including aspirin 100 mg OD, plus clopidogrel 75 mg OD, or prasugrel 10 mg OD, or ticagrelor 90 mg BID) were prospectively enrolled before cessation of the P2Y12inhibitor therapy. MiRNA-223, -150, -21 and -126 were determined at baseline (=last day of P2Y12-inhibitor intake) and 10, 30 and 180 days thereafter. Results: Cessation of P2Y12-inhibitor therapy did not significantly change miRNA levels. However, in ticagrelor-treated patients, miRNA levels were significantly increased at baseline (miRNA-223 and -21), day 10 (miRNA-223, -150, -21, -126) and day 30 (miRNA-223, -150, -21, -126) as compared to prasugrel, and at day 10 (miRNA-150 and -21) and day 30 (miRNA-150) as compared to clopidogrel (all P < 0.05). At day 180, only miRNA-126 levels differed significantly with respect to the P2Y12 inhibitor used (P < 0.05). After adjustment for confounders, choice of P2Y12-inhibitor was the strongest predictor of miRNA levels (P < 0.001), while cessation of P2Y12-inhibitor therapy did not significantly impact miRNA levels. Conclusion: In patients with CAD, ticagrelor intake is associated with increased levels of platelet miRNAs as compared to clopidogrel and prasugrel. Platelet miRNAs are not useful to monitor platelet function after cessation of P2Y12 inhibitors. K E Y W O R D Sdual antiplatelet therapy, micro-RNA, P2Y12 inhibitor, platelet micro-RNA, prasugrel, ticagrelor Note: Therapy group (choice of P2Y12 inhibitor) was the strongest predictor of miRNA expression levels after correction for known and identified baseline differences. Time point did not significantly impact on miRNA levels.

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“…In the case of peripheral artery disease (PAD) ISR, the role of 11 restenosis-related circulating miRNAs was examined in a primary endpoint constituted by target lesion restenosis (TLR) and atherothrombotic events, and a secondary endpoint represented by target vessel revascularization (TVR) (Stojkovic et al, 2018). Findings showed that miRNA-92a and miRNA-195 were independent predictors of the primary endpoint, but only miRNA-195 was able to independently predict TVR.…”

Section: Circulating Mirnas As Restenosis Biomarkersmentioning

confidence: 99%

The Current State of MicroRNAs as Restenosis Biomarkers

et al. 2020

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In-stent restenosis corresponds to the diameter reduction of coronary vessels following percutaneous coronary intervention (PCI), an invasive procedure in which a stent is deployed into the coronary arteries, producing profuse neointimal hyperplasia. The reasons for this process to occur still lack a clear answer, which is partly why it remains as a clinically significant problem. As a consequence, there is a vigorous need to identify useful non-invasive biomarkers to differentiate and follow-up subjects at risk of developing restenosis, and due to their extraordinary stability in several bodily fluids, microRNA research has received extensive attention to accomplish this task. This review depicts the current understanding, diagnostic potential and clinical challenges of microRNA molecules as possible blood-based restenosis biomarkers.

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Circulating microRNAs identify patients at increased risk of in-stent restenosis after peripheral angioplasty with stent implantation

Cited by 35 publications

References 60 publications

MicroRNA and Cardiovascular Diseases

MicroRNA and Cardiovascular Diseases

Course of platelet miRNAs after cessation of P2Y12 antagonists

The Current State of MicroRNAs as Restenosis Biomarkers

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