MicroRNA Expression Pattern in Patients with Ventricular Tachycardia and End-Stage Heart Failure

Calway, Tyler; Bak, Trevor; Kim, G.H.

doi:10.1016/j.healun.2015.01.763

Cited by 3 publications

(5 citation statements)

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“…The role of exosomes in arrhythmia may be related to miRNAs that regulate calcium signaling and, thus, cardiac conduction and contraction. For instance, cardiomyocytederived exosomes are enriched in miR-1, miR-133 and miR-328 after ischemia, a known proarrhythmic factor [148][149][150]. These miRNAs regulate the function of key regulatory proteins of calcium signaling, such as Ca 2+ /calmodulin-dependent protein kinase II and L-type calcium channels, which regulate cardiac conduction and action potentials [151].…”

Section: Disorders Of the Rhythmmentioning

confidence: 99%

“…These EVs can also be used to treat complications associated to diabetes and obesity. For instance, miR-486 enclosed in these EVs has been found to alleviate diabetic nephropathy in vivo, while bone marrow MSC-derived exosomes improve bone regeneration, which is impaired in obesity [149,150].…”

Section: Drug Delivery Systems For Specific Targeting Towards Cardiometabolic Diseasesmentioning

confidence: 99%

“…Circulating exosomes and exosomes derived from adipose tissue may also be enriched with miRNAs that regulate metabolic function in obesity and diabetes. In particular, it has been found that exosomes derived from healthy individuals and brown adipose tissue reduce body weight, lower blood glucose and alleviate lipid accumulation in vivo [150][151][152]. Nonetheless, modifications to exosome content and structure can generate a more efficient delivery system, which can be tailored to target specific cell types in the appropriate clinical setting.…”

Section: Drug Delivery Systems For Specific Targeting Towards Cardiometabolic Diseasesmentioning

confidence: 99%

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Potential Applications and Functional Roles of Exosomes in Cardiometabolic Disease

et al. 2021

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Despite diagnostic and therapeutic advances, cardiometabolic disease remains the leading cause of death worldwide. Extracellular vesicles (EVs), which include exosomes and microvesicles, have gained particular interest because of their role in metabolic homeostasis and cardiovascular physiology. Indeed, EVs are recognized as critical mediators of intercellular communication in the cardiovascular system. Exosomes are naturally occurring nanocarriers that transfer biological information in the setting of metabolic abnormalities and cardiac dysfunction. The study of these EVs can increase our knowledge on the pathophysiological mechanisms of metabolic disorders and their cardiovascular complications. Because of their inherent properties and composition, exosomes have been proposed as diagnostic and prognostic biomarkers and therapeutics for specific targeting and drug delivery. Emerging fields of study explore the use exosomes as tools for gene therapy and as a cell-free alternative for regenerative medicine. Furthermore, innovative biomaterials can incorporate exosomes to enhance tissue regeneration and engineering. In this work, we summarize the most recent knowledge on the role of exosomes in cardiometabolic pathophysiology while highlighting their potential therapeutic applications.

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Section: Disorders Of the Rhythmmentioning

confidence: 99%

Section: Drug Delivery Systems For Specific Targeting Towards Cardiometabolic Diseasesmentioning

confidence: 99%

Section: Drug Delivery Systems For Specific Targeting Towards Cardiometabolic Diseasesmentioning

confidence: 99%

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Potential Applications and Functional Roles of Exosomes in Cardiometabolic Disease

et al. 2021

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“…Previous studies have shown miR-130a to be upregulated in myocardium of patients with heart failure [19,20]. Furthermore, our recent analysis of heart failure patient samples found that miR-130a is significantly upregulated in patients who exhibited ventricular arrhythmias [21]. In this study, we investigated miR-130a regulation of Desmocollin 2 (DSC2) gene expression, as it has a predicted target site for miR-130a.…”

Section: Introductionmentioning

confidence: 98%

MicroRNA-130a Regulation of Desmocollin2 in a Novel Model of Arrhythmogenic Cardiomyopathy

Mazurek¹,

Calway²,

Harmon³

et al. 2015

Journal of Cardiac Failure

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“…Previous studies have shown miR-130a to be upregulated in myocardium of patients with heart failure [19, 20]. Furthermore, our recent analysis of heart failure patient samples found that miR-130a is significantly upregulated in patients who exhibited ventricular arrhythmias [21]. In this study, we investigated miR-130a regulation of Desmocollin 2 (DSC2) gene expression, as it has a predicted target site for miR-130a.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-130a Regulation of Desmocollin 2 in a Novel Model of Arrhythmogenic Cardiomyopathy

Mazurek

Calway

Harmon

et al. 2017

MIRNA

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Background MicroRNAs are small noncoding RNA molecules that play a critical role in regulating physiological and disease processes. Recent studies have now recognized microRNAs as an important player in cardiac arrhythmogenesis. Molecular insight into arrhythmogenic cardiomyopathy (AC) has primarily focused on mutations in desmosome proteins. To our knowledge, models of AC due to microRNA dysregulation have not been reported. Previously, we reported on miR-130a mediated down-regulation of Connexin43. Objective Here, we investigate miR-130a-mediated translational repression of Desmocollin2 (DSC2), as it has a predicted target site for miR-130a. DSC2 is an important protein for cell adhesion, which has been shown to be dysregulated in human AC. Results After induction of miR-130a, transgenic mice demonstrated right ventricular dilation. Surface ECG revealed spontaneous premature ventricular complexes confirming an arrhythmogenic phenotype in αMHC-miR130a mice. Using total protein from whole ventricular lysate, western blot analysis demonstrated an 80% reduction in DSC2 levels in transgenic myocardium. Furthermore, immunofluorescent staining confirmed downregulation of DSC2 in transgenic compared with littermate control myocardium. In transgenic hearts, histologic findings revealed fibrosis and lipid accumulation within both ventricles. To validate DSC2 as a direct target of miR-130a, we performed in vitro target assays in 3T3 fibroblasts, known to express miR-130a. Using a luciferase reporter fused to the 3′UTR of DSC2 compared with a control, we found a 42% reduction in luciferase activity with the DSC2 3′UTR. This reduction was reversed upon selective inhibition of miR-130a. Conclusion Overexpression of miR-130a results in a disease phenotype characteristic of AC and therefore, may serve as potential model for microRNA-induced AC.

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MicroRNA Expression Pattern in Patients with Ventricular Tachycardia and End-Stage Heart Failure

Cited by 3 publications

References 0 publications

Potential Applications and Functional Roles of Exosomes in Cardiometabolic Disease

Potential Applications and Functional Roles of Exosomes in Cardiometabolic Disease

MicroRNA-130a Regulation of Desmocollin2 in a Novel Model of Arrhythmogenic Cardiomyopathy

MicroRNA-130a Regulation of Desmocollin 2 in a Novel Model of Arrhythmogenic Cardiomyopathy

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