MicroRNAs in Valvular Heart Diseases: Potential Role as Markers and Actors of Valvular and Cardiac Remodeling

Oury, Cécile; Servais, Laurence; Bouznad, Nassim; Hego, Alexandre; Nchimi, Alain; Lancellotti, Patrizio

doi:10.3390/ijms17071120

Cited by 39 publications

(42 citation statements)

References 73 publications

(90 reference 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: 94%

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: 94%

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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“…As a result, it has been suggested that miRs could serve as potential diagnostic biomarkers for a multitude of pathologies in humans. Recent studies have revealed that aberrant miR expression profiles are associated with a variety of cardiovascular pathologies including hypertrophy, heart failure, arrhythmias and AMI (19,20). Indeed, increased circulating levels of several myomiRs (miRNA-1, -19, -133a, -133b) which are highly expressed in skeletal muscle, as well as in the heart, were recorded (21).…”

Section: Discussionmentioning

confidence: 99%

Expression of miR-208b and miR-499 in Greek Patients with Acute Myocardial Infarction

Αγιαννιτόπουλος

Pavlopoulou

Tsamis

et al. 2018

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Abstract. Background/Aim: Certain microRNAs (miRs) present in human plasma are candidate biomarkers for cardiovascular diseases, including acute myocardial infarction (AMI). We examined the expression of two cardiac-specific miRs (miR-208b and miR-499) MicroRNAs (miRs) are evolutionary small endogenous, noncoding, single-stranded RNAs involved in the regulation of gene expression at the post-transcriptional level (1). They possess an important role in multiple biological processes by binding to their target mRNAs and altering the protein expression of their candidate targets (2). Circulating miRs detected in serum or plasma, are actively secreted in macrovesicles or exosomes from different cell types (3), including cardiomyocytes. Elevated mRNA expression levels have been involved in numerous human pathologies including cardiovascular diseases (4).Acute myocardial infarction (AMI) is the acute necrosis of myocardial tissue due to persistent and severe ischemia, and remains a leading cause of morbidity and mortality worldwide (5). Accurate and rapid diagnosis is crucial for the clinical management and prognosis of AMI (6). Thus, exploration of new potential biomarkers that will contribute in this direction is particularly important. Although the circulating levels of cardiac troponin proteins are currently regarded as the most prominent biomarkers for the diagnosis of AMI, measurable amounts of troponins are not usually released from damaged myocardium earlier than 4-8 h after the onset of symptoms (6, 7). In contrast, the levels of circulating plasma miRs can be measured rapidly using realtime PCR, offering two main advantages over standard antibody-based assays: increased sensitivity and specificity. Several studies have already considered circulating cardiacspecific or -enriched miRs as new biomarkers for the early diagnosis of .In fact, the vast majority of these studies have been performed in Asian populations, while limited studies from European populations are also available (12). Consequently, better validation through larger studies is required for the establishment of miRs as biomarkers in clinical practice. Based on the elegant study of Huang et al. (13) who showed that miRNA expression levels exhibit population differences, and the recorded dysregulation of two specific myocardialderived miRNAs in AMI patients (14, 15), we decided to further investigate their expression in a Caucasian population. Specifically, the purpose of this study was to 313

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“…120 Circulating miRNA may be involved in critical biological processes underlying cardiovascular disorders and are currently being investigated as biomarkers in cardiovascular disease. 121 Examples of potential miRNA biomarkers in AS include miR-133a, which was shown to predict the extent of regression of LV hypertrophy after SAVR 122 ; miR-21, which was shown to be associated with LV fibrosis 123 ; and miR-210, which was independently associated with mortality in patients with moderate-to-severe AS. 124 miRNA research is expected to expand considerably in the coming years, and new candidate biomarkers will likely be identified.…”

Section: Markers Of Alteration In Cardiac Metabolismmentioning

confidence: 99%

“…124 miRNA research is expected to expand considerably in the coming years, and new candidate biomarkers will likely be identified. 121 …”

Section: Markers Of Alteration In Cardiac Metabolismmentioning

confidence: 99%

Biomarkers in Aortic Stenosis: A Systematic Review

et al. 2017

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Aortic stenosis (AS) is one of the most common heart valve diseases among adults. When symptoms develop alongside severe AS, there is a poor prognosis unless aortic valve replacement (AVR) is performed; however, many patients do not report symptoms even when AS is severe. The optimal timing of AVR for these patients remains uncertain and controversial. AS is a heterogeneous disease with a complex pathophysiology involving structural and biological changes of the valve as well as adaptive and maladaptive compensatory changes in the myocardium and vasculature in response to chronic pressure overload. Several biomarkers reflecting these processes have been identified and have shown to have utility in predicting symptom onset and clinical events before and after AVR. Herein we systematically review biomarkers that have been studied in the setting of AS and summarize their potential use for risk stratification and ultimately to guide the optimal timing of AVR.

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MicroRNAs in Valvular Heart Diseases: Potential Role as Markers and Actors of Valvular and Cardiac Remodeling

Cited by 39 publications

References 73 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

Expression of miR-208b and miR-499 in Greek Patients with Acute Myocardial Infarction

Biomarkers in Aortic Stenosis: A Systematic Review

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