ArticleCirculation2016
Genotype-Dependent and -Independent Calcium Signaling Dysregulation in Human Hypertrophic Cardiomyopathy.
Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 97 citations in OpenAlex.
- Mapping Gene Expression to an Interpretable Semantic Space.bioRxiv : the preprint server for biology · 2026Article
- Atrial electrophysiology in hypertrophic cardiomyopathy: current insights and knowledge gaps.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2026Review
- SGLT2 Inhibitors in Hypertrophic Cardiomyopathy: Emerging Evidence and Putative Mechanisms.Biomolecules · 2026Review
- Article
- Hypercontractility and Oxidative Stress Drive Creatine Kinase Dysfunction in Hypertrophic Cardiomyopathy.Circulation · 2025Article
- Evaluation of sudden cardiac death in hypertrophic cardiomyopathy.Journal of cardiovascular imaging · 2025Review
- Mechano-energetic uncoupling in heart failure.Nature reviews. Cardiology · 2025Review
- Tailored therapeutics for cardiomyopathies.Nature reviews. Cardiology · 2025Review
- Dysregulation of N-terminal acetylation causes cardiac arrhythmia and cardiomyopathy.Nature communications · 2025Article
- An Integrated Network Pharmacology and RNA-seq Approach for Exploring the Protective Effect of Isoquercitrin in Doxorubicin-Induced Cardiotoxicity: Identification of Novel Genes.Cardiovascular toxicology · 2025Article
- Growth-Associated Protein-43 Loss Promotes CaAntioxidants (Basel, Switzerland) · 2025Article
- Hypertrophic Cardiomyopathy-Associated CRYABInternational journal of molecular sciences · 2025Article
- Obstructive hypertrophic cardiomyopathy: from genetic insights to a multimodal therapeutic approach with mavacamten, aficamten, and beyond.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024Review
- Review
- Reduced connexin-43 expression, slow conduction and repolarisation dispersion in a model of hypertrophic cardiomyopathy.Disease models & mechanisms · 2024Article
- Substrate mechanics unveil early structural and functional pathology in iPSC micro-tissue models of hypertrophic cardiomyopathy.iScience · 2024Article
- Role of Genetics in Diagnosis and Management of Hypertrophic Cardiomyopathy: A Glimpse into the Future.Biomedicines · 2024Review
- Current perspectives of sudden cardiac death management in hypertrophic cardiomyopathy.Heart failure reviews · 2024Review
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- RYR2 deficient human model identifies calcium handling and metabolic dysfunction impacting pharmacological responses.Frontiers in cardiovascular medicine · 2024Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAberrant calcium signaling may contribute to arrhythmias and adverse remodeling in hypertrophic cardiomyopathy (HCM). Mutations in sarcomere genes may distinctly alter calcium handling pathways.
methodsWe analyzed gene expression, protein levels, and functional assays for calcium regulatory pathways in human HCM surgical samples with (n=25) and without (n=10) sarcomere mutations compared with control hearts (n=8).
resultsGene expression and protein levels for calsequestrin, L-type calcium channel, sodium-calcium exchanger, phospholamban, calcineurin, and calcium/calmodulin-dependent protein kinase type II (CaMKII) were similar in HCM samples compared with controls. CaMKII protein abundance was increased only in sarcomere-mutation HCM (P<0.001). The CaMKII target pT17-phospholamban was 5.5-fold increased only in sarcomere-mutation HCM (P=0.01), as was autophosphorylated CaMKII (P<0.01), suggestive of constitutive activation. Calcineurin (PPP3CB) mRNA was not increased, nor was RCAN1 mRNA level, indicating a lack of calcineurin activation. Furthermore, myocyte enhancer factor 2 and nuclear factor of activated T cell transcription factor activity was not increased in HCM, suggesting that calcineurin pathway activation is not an upstream cause of increased CAMKII protein abundance or activation. SERCA2A mRNA transcript levels were reduced in HCM regardless of genotype, as was sarcoplasmic endoplasmic reticular calcium ATPase 2/phospholamban protein ratio (45% reduced; P=0.03).
conclusionsHuman HCM demonstrates calcium mishandling through both genotype-specific and common pathways. Posttranslational activation of the CaMKII pathway is specific to sarcomere mutation-positive HCM, whereas sarcoplasmic endoplasmic reticular calcium ATPase 2 abundance and sarcoplasmic reticulum Ca uptake are depressed in both sarcomere mutation-positive and -negative HCM.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.