Circulating Levels of MicroRNAs in Hypertrophic Cardiomyopathy: The Relationship With Left Ventricular Hypertrophy, Left Atrial Dilatation and Ventricular Depolarisation-Repolarisation Parameters

Sonsöz, Mehmet Rasih; Yılmaz, Mustafa; Çevik, Erdem; Orta, Huseyin; Bilge, Ahmet Kaya; Elıtok, Ali; Onur, Imran; Kömürcü-Bayrak, Evrim

doi:10.1016/j.hlc.2021.04.019

Cited by 3 publications

(4 citation statements)

References 28 publications

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“…Previous evidence has pointed out the critical involvement of miRNA 30-5p, 23a-3p and miRNA 451a in pathological cardiac remodeling following acute myocardial infarction, chronic cardiomyopathies or in heart failure [ 12 , 15 , 18 , 22 , 25 ]. Under physiological conditions, these miRNAs down-regulate autophagy and apoptosis of cardiomyocytes and modulate collagen balance.…”

Section: Discussionmentioning

confidence: 99%

A small circulating miRNAs signature predicts mortality and adverse cardiovascular outcomes in chronic hemodialysis patients

Bolignano

Greco

Presta

et al. 2023

Clinical Kidney Journal

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Background Chronic hemodialysis (HD) patients exhibit severe morpho-functional cardiac alterations, posing them at a high risk of death and adverse cardiovascular (CV) outcomes. Despite an unbalanced expression of various microRNAs (miRNAs) has been related to pathological cardiac remodelling and worse CV outcomes, scarce evidence exist on their role in this setting. Methods We evaluated circulating levels of a selected miRNAs panel (30a-5p, 23a-3p, 451a and let7d-5p) in 74 chronic HD patients together with a thorough clinical and echocardiography assessment. Individuals were then prospectly followed (median 22 mo.). The primary endpoint was a composite of all-cause and CV mortality and non-fatal CV events. Results Circulating levels of all miRNAs were lower in HD patients as compared to healthy controls and independently correlated to the severity of cardiac dysfunction. miRNA 30a-5p, 23a-3p and 451a expression was even lower in 30 subjects (40.5%) reaching the composite endpoint (p<0.001), while no differences were reported for let7d-5p. The predictive value of these miRNAs was supported by univariate followed by multivariate Cox-regression analyses (HR ranging from 0.943 to 0.995; p = 0.05 to 0.02) while Kaplan-Meier analyses confirmed a faster progression to the endpoint in individuals displaying miRNA levels below an optimal ROC-derived cut-off value (p ranging from 0.001 to <0.0001; crude HRs 7.95 to 8.61). Conclusions Lower circulating levels of miRNA 30-5p, 23a-3p and 451a in HD patients may reflect cardiac abnormalities and predict a higher risk of worse clinical outcomes in the short-mid term. Future studies on larger HD populations are needed to generalize these findings.

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Section: Discussionmentioning

confidence: 99%

A small circulating miRNAs signature predicts mortality and adverse cardiovascular outcomes in chronic hemodialysis patients

Bolignano

Greco

Presta

et al. 2023

Clinical Kidney Journal

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“…miR-29a is also part of a family of microRNAs’ which target a group of functionally related genes involved in apoptosis ( Tcd1 , Mcl1 , p85a , CDC42 , YY1 , CDK6 ), cell differentiation ( YY1 , HDAC4 ), regulation of the extracellular matrix proteins ( Collegen ( I , III , IV ), LAMC1 , FBN1 , ELN , MMP2 , ITGB1 ) and immune responses ( B7-H3 , Interferon-γ ) [ 127 ]. In cardiovascular diseases it has been linked to bicuspid aortic valve disorders [ 67 ], hypertrophic cardiomyopathy [ 68 , 69 , 62 ], coronary heart disease [ 70 , 71 ], valvular heart disease [ 72 ], cardiac fibrosis [ 73 ], left ventricular remodelling [ 74 ] and pulmonary arterial hypertension [ 75 ]. The levels of circulating miR-29a are also thought to be linked to haemolysis of blood cells linked to certain cardiac pathologies rather than directly secreted only from the cardiomyocyte cells [ 128 ].…”

Section: Resultsmentioning

confidence: 99%

A systematic review of miRNAs as biomarkers for chemotherapy-induced cardiotoxicity in breast cancer patients reveals potentially clinically informative panels as well as key challenges in miRNA research

Brown¹,

Mantzaris

Nicolaou³

et al. 2022

Cardio-Oncology

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Breast cancer patients are at a particularly high risk of cardiotoxicity from chemotherapy having a detrimental effect on quality-of-life parameters and increasing the risk of mortality. Prognostic biomarkers would allow the management of therapies to mitigate the risks of cardiotoxicity in vulnerable patients and a key potential candidate for such biomarkers are microRNAs (miRNA). miRNAs are post-transcriptional regulators of gene expression which can also be released into the circulatory system and have been associated with the progression of many chronic diseases including many types of cancer. In this review, the evidence for the potential application of miRNAs as biomarkers for chemotherapy-induced cardiotoxicity (CIC) in breast cancer patientsis evaluated and a simple meta-analysis is performed to confirm the replication status of each reported miRNA. Further selection of miRNAs is performed by reviewing the reported associations of each miRNA with other cardiovascular conditions. Based on this research, the most representative panels targeting specific chemotherapy agents and treatment regimens are suggested, that contain several informative miRNAs, including both general markers of cardiac damage as well as those for the specific cancer treatments.

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“…9,10 There have been several studies investigating circulating miRNAs in HCM, but these studies are limited by small numbers of study participants, are performed in highly heterogenous HCM populations, describe expression of a small number of preselected miRNAs, and do not consider the influence of sarcomere gene variants. [11][12][13][14][15] The purpose of this study was to use a nonbiased array approach to investigate whether circulating miRNAs could serve as a clinical stratification biomarker for sarcomeric variant carriers with subclinical and clinical HCM.…”

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confidence: 99%

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confidence: 99%

Circulating MicroRNAs Identify Early Phenotypic Changes in Sarcomeric Hypertrophic Cardiomyopathy

Sucharov

Neltner

Pietra

et al. 2023

Circ: Heart Failure

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Background: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. Pathogenic germline variation in genes encoding the sarcomere is the predominant cause of disease. However diagnostic features, including unexplained left ventricular hypertrophy, typically do not develop until late adolescence or after. The early stages of disease pathogenesis and the mechanisms underlying the transition to a clinically overt phenotype are not well understood. In this study, we investigated if circulating microRNAs (miRNAs) could stratify disease stage in sarcomeric HCM. Methods: We performed arrays for 381 miRNAs using serum from HCM sarcomere variant carriers with and without a diagnosis of HCM and healthy controls. To identify differentially expressed circulating miRNAs between groups, multiple approaches were used including random forest, Wilcoxon rank sum test, and logistic regression. The abundance of all miRNAs was normalized to miRNA-320. Results: Of 57 sarcomere variant carriers, 25 had clinical HCM and 32 had subclinical HCM with normal left ventricular wall thickness (21 with early phenotypic manifestations and 11 with no discernible phenotypic manifestations). Circulating miRNA profile differentiated healthy controls from sarcomere variant carriers with subclinical and clinical disease. Additionally, circulating miRNAs differentiated clinical HCM from subclinical HCM without early phenotypic changes; and subclinical HCM with and without early phenotypic changes. Circulating miRNA profiles did not differentiate clinical HCM from subclinical HCM with early phenotypic changes, suggesting biologic similarity between these groups. Conclusions: Circulating miRNAs may augment the clinical stratification of HCM and improve understanding of the transition from health to disease in sarcomere gene variant carriers.

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Circulating Levels of MicroRNAs in Hypertrophic Cardiomyopathy: The Relationship With Left Ventricular Hypertrophy, Left Atrial Dilatation and Ventricular Depolarisation-Repolarisation Parameters

Cited by 3 publications

References 28 publications

A small circulating miRNAs signature predicts mortality and adverse cardiovascular outcomes in chronic hemodialysis patients

A small circulating miRNAs signature predicts mortality and adverse cardiovascular outcomes in chronic hemodialysis patients

A systematic review of miRNAs as biomarkers for chemotherapy-induced cardiotoxicity in breast cancer patients reveals potentially clinically informative panels as well as key challenges in miRNA research

Circulating MicroRNAs Identify Early Phenotypic Changes in Sarcomeric Hypertrophic Cardiomyopathy

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