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

Karakas, Mahir; Schulte, Christian; Appelbaum, Sebastian; Ojeda, Francisco; Lackner, Karl J.; Münzel, Thomas; Schnabel, Renate B.; Blankenberg, Stefan; Zeller, Tanja

doi:10.1093/eurheartj/ehw250

Cited by 122 publications

(118 citation statements)

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“…Matrix vesicles contribute to calcification by carrying and depositing calcium crystals [33]. MicroRNAs are roughly 22 nucleotides long, singlestranded molecules that function to regulate gene expression by binding to mRNA, usually in the 3'UTR, to decrease mRNA translation and stability [34], microRNAs have also been found to play an important role in cardiovascular diseases [35][36][37][38][39]. We have found high enrichment of microRNAs after 20 days of Lp (a) treatment in HAVICs.…”

Section: Discussionmentioning

confidence: 95%

Gene Expression and Proteomic Profiling of Lp (a)-Induced Signalling Pathways in Human Aortic Valve Interstitial Cells

Yu¹,

Kapur²,

Hamid³

et al. 2018

J Pharmacogenomics Pharmacoproteom

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Aortic valve stenosis is one of the most common valve diseases in the world for which there is currently no pharmacological treatment to prevent or halt disease progression. Recent genetic research has demonstrated a causal association between elevated blood levels of lipoprotein (a) (Lp (a)) and aortic valve calcification, however, the mechanisms by which Lp (a) contributes to aortic valve calcification and stenosis, is unknown. In the present study, we aimed at determining Lp (a)-induced changes in human aortic valve interstitial cells using an integrated bioinformatics approach. The Lp (a)-induced cellular pathways were analysed using microarray gene expression and proteomic data from non-stenotic human aortic valve interstitial cells. Lp (a) treatment induced osteogenic differentiation, extracellular remodeling, extracellular vesicles biogenesis, and apoptosis of human aortic valve interstitial cells. In particular, the Wnt/ β-catenin signalling pathway, a known calcification pathway contributing to aortic valve stenosis, was differentially expressed compared to non-treated cells. Lp (a) also induced the expression of 14-3-3 proteins known to regulate various signalling pathway relevant to aortic valve disease. Elucidating the mechanisms and molecular players that Lp (a) induces in the early stages of the disease to initiate aortic valve calcification could provide insight into potential pharmacological targets for the treatment of this debilitating disease.

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Section: Discussionmentioning

confidence: 95%

Gene Expression and Proteomic Profiling of Lp (a)-Induced Signalling Pathways in Human Aortic Valve Interstitial Cells

Yu¹,

Kapur²,

Hamid³

et al. 2018

J Pharmacogenomics Pharmacoproteom

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show abstract

“…Latest results with respect to prognostic miRNA evaluation in MI report a set of five miRNAs associated with future MI in the HUNT study [32], while a set of seven miRNAs was identified to reliably predict cardiovascular death in patients with CAD in the AtheroGene study [30]. The first data from a large-scale study were reported by Zampetaki et al in 2012 [97].…”

Section: Mirnas In Prediction and Prognosis Of Coronary Artery Diseasmentioning

confidence: 99%

microRNAs in cardiovascular disease – clinical application

Schulte

Karakas

Zeller

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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107

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microRNAs (miRNAs) are well-known, powerful regulators of gene expression, and their potential to serve as circulating biomarkers is widely accepted. In cardiovascular disease (CVD), numerous studies have suggested miRNAs as strong circulating biomarkers with high diagnostic as well as prognostic power. In coronary artery disease (CAD) and heart failure (HF), miRNAs have been suggested as reliable biomarkers matching up to established protein-based such as cardiac troponins (cT) or natriuretic peptides. Also, in other CVD entities, miRNAs were identified as surprisingly specific biomarkers -with great potential for clinical applicability, especially in those entities that lack specific protein-based biomarkers such as atrial fibrillation (AF) and acute pulmonary embolism (APE). In this regard, miRNA signatures, comprising a set of miRNAs, yield high sensitivity and specificity. Attempts to utilize miRNAs as therapeutic agents have led to promising results. In this article, we review the clinical applicability of circulating miRNAs in CVD. We are giving an overview of miRNAs as biomarkers in numerous CVD entities to depict the variety of their potential clinical deployment. We illustrate the function of miRNAs by means of single miRNA examples in CVD.

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“…Additionally, since UAP is atherosclerosis without substantial ischemia, some overlap with previously found markers for SAP in earlier studies would have been expected. However, none of the eight microRNAs that were measured in the study of Karakas et al (4) were found in a total of 17 earlier studies on SAP markers (12). Although, the study of Zeller et al (5) is the first to consistently show an association of microRNAs with UAP in three independent cohorts, we maintain to wonder why so many different study of microRNA biomarkers produce different results.…”

Section: Relation To Other Micrornas Studiesmentioning

confidence: 90%

Circulating microRNA biomarkers for cardiovascular risk prediction: are we approaching clinical application?

2016

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

Cited by 122 publications

References 20 publications

Gene Expression and Proteomic Profiling of Lp (a)-Induced Signalling Pathways in Human Aortic Valve Interstitial Cells

Gene Expression and Proteomic Profiling of Lp (a)-Induced Signalling Pathways in Human Aortic Valve Interstitial Cells

microRNAs in cardiovascular disease – clinical application

Circulating microRNA biomarkers for cardiovascular risk prediction: are we approaching clinical application?

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