The L-type Ca<sup>2+</sup> channel: A mediator of hypertrophic cardiomyopathy

Viola, Helena M.; Hool, Livia C.

doi:10.1080/19336950.2016.1213053

Cited by 8 publications

(4 citation statements)

References 8 publications

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“…Activation of the L-type Ca 2+ current ( I CaL ) increases intracellular Ca 2+ concentration, which promotes mitochondrial uptake, resulting in elevated production of mtROS, which in turn leads to sustained I CaL activation [ 44 ]. To investigate a possible activation of the I CaL by mtROS, we performed whole-cell patch clamp recordings from acutely isolated ventricular cardiomyocytes from Nox4 TG618 and wild-type mice ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial oxidative stress contributes to diastolic dysfunction through impaired mitochondrial dynamics

Lozhkin¹,

Vendrov²,

Ramos-Mondragón³

et al. 2022

Redox Biology

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Section: Resultsmentioning

confidence: 99%

Mitochondrial oxidative stress contributes to diastolic dysfunction through impaired mitochondrial dynamics

Lozhkin¹,

Vendrov²,

Ramos-Mondragón³

et al. 2022

Redox Biology

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“…The interesting fact that the prolonged QTc did not find attention during clinical routine but was revealed after in vitro studies supports the view for more personalized medicine. Given the relevant frequency of QTc prolongation in HCM and the possibility that other HCM mutations as well as myocardial disarray in a more general sense may affect LTCC activity (Viola & Hool, 2017), future work should be directed toward answering whether the beneficial effects of diltiazem treatment observed in our study and in a previously published pilot study (Ho et al, 2015) may in fact relate to a general mechanism of HCM pathology or might be specific due to altered interaction between aactinin 2 and the LTCC, as indicated by our BRET analysis and recently identified (Tseng et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Disease modeling of a mutation in α‐actinin 2 guides clinical therapy in hypertrophic cardiomyopathy

et al. 2019

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Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease accompanied by structural and contractile alterations. We identified a rare c.740C>T (p.T247M) mutation in ACTN2, encoding α‐actinin 2 in a HCM patient, who presented with left ventricular hypertrophy, outflow tract obstruction, and atrial fibrillation. We generated patient‐derived human‐induced pluripotent stem cells (hiPSCs) and show that hiPSC‐derived cardiomyocytes and engineered heart tissues recapitulated several hallmarks of HCM, such as hypertrophy, myofibrillar disarray, hypercontractility, impaired relaxation, and higher myofilament Ca2+ sensitivity, and also prolonged action potential duration and enhanced L‐type Ca2+ current. The L‐type Ca2+ channel blocker diltiazem reduced force amplitude, relaxation, and action potential duration to a greater extent in HCM than in isogenic control. We translated our findings to patient care and showed that diltiazem application ameliorated the prolonged QTc interval in HCM‐affected son and sister of the index patient. These data provide evidence for this ACTN2 mutation to be disease‐causing in cardiomyocytes, guiding clinical therapy in this HCM family. This study may serve as a proof‐of‐principle for the use of hiPSC for personalized treatment of cardiomyopathies.

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“…These two circRNAs exhibited high levels of calcium release channel activity. Since disturbance of calcium homeostasis is one of the most prevalent causes, mutation-specific alterations in the rate of calcium release in HCM are closely correlated with the disease [35][36][37][38][39]. Additionally, calcium homeostasis abnormalities may worsen diastolic dysfunction, resulting in heart failure and substantial morbidity and mortality [40][41][42].…”

Section: Plos Onementioning

confidence: 99%

Identification of circRNA-miRNA-mRNA regulatory network and its role in cardiac hypertrophy

et al. 2023

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Background Hypertrophic cardiomyopathy (HCM) is a grave hazard to human health. Circular RNA (circRNAs) and micro RNA (miRNAs), which are competitive endogenous RNA, have been shown to play a critical role inHCM pathogenicity. However, to a great extent, the biological activities of ceRNA in HCM pathophysiology and prognosis remain to be investigated. Materials and methods By analyzing the expression files in the Gene Expression Comprehensive (GEO) database, differentially expressed (DE) circRNAs, miRNAs, and mRNAs in HCM were identified, and the target molecules of circRNAs and miRNAs were predicted. The intersection of the differentially expressed RNA molecules and the expected target was then calculated, and a ceRNA network was subsequently constructed using RNA molecules. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the potential etiology was elucidated. qPCR was used to validate a portion of the hub gene using Angiotensin II to generate a cell hypertrophy model. Results Three large-scale HCM sample datasets were extracted from the GEO database. After crossing these molecules with their expected targets, the circRNA-miRNA-mRNA network had two DEcircRNAs, two DEmiRNAs, and thirty DEmRNAs, compared to normal tissues. Functional enrichment analysis of GO and KEGG demonstrated that many of the HCM pathways and mechanisms were associated with calcium channel release, which is also the primary focus of future research. The qPCR results revealed that circRNA, miRNA, and mRNA expression levels were different. They may include novel noninvasive indicators for the early screening and prognostic prediction of HCM. Conclusion In this study, we hypothesized a circRNA-miRNA-mRNA regulation network that is closely related to the progression and clinical outcomes of HCM and may contain promising biomarkers and treatment targets for HCM.

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The L-type Ca²⁺ channel: A mediator of hypertrophic cardiomyopathy

Cited by 8 publications

References 8 publications

Mitochondrial oxidative stress contributes to diastolic dysfunction through impaired mitochondrial dynamics

Mitochondrial oxidative stress contributes to diastolic dysfunction through impaired mitochondrial dynamics

Disease modeling of a mutation in α‐actinin 2 guides clinical therapy in hypertrophic cardiomyopathy

Identification of circRNA-miRNA-mRNA regulatory network and its role in cardiac hypertrophy

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The L-type Ca2+ channel: A mediator of hypertrophic cardiomyopathy

Cited by 8 publications

References 8 publications

Mitochondrial oxidative stress contributes to diastolic dysfunction through impaired mitochondrial dynamics

Mitochondrial oxidative stress contributes to diastolic dysfunction through impaired mitochondrial dynamics

Disease modeling of a mutation in α‐actinin 2 guides clinical therapy in hypertrophic cardiomyopathy

Identification of circRNA-miRNA-mRNA regulatory network and its role in cardiac hypertrophy

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The L-type Ca²⁺ channel: A mediator of hypertrophic cardiomyopathy