ArticleCirculation2012
Targeted sarcoplasmic reticulum Ca2+ ATPase 2a gene delivery to restore electrical stability in the failing heart.
Article in Circulation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 104 citations in OpenAlex.
- Trial
- Early Right Ventricular Apical Pacing-Induced Gene Expression Alterations Are Associated with Deterioration of Left Ventricular Systolic Function.Disease markers · 2017Trial
- The interaction between sarcoplasmic reticulum and mitochondria: a novel mechanism for cardiac arrhythmia.Frontiers in physiology · 2026Review
- Cardiomyocyte-Specific RNF128 Attenuates Pathological Cardiac Hypertrophy Progression by Stabilizing SERCA2a through Lys63-Linked Polyubiquitination.Theranostics · 2026Article
- Metabolic-Electrophysiological Coupling in Heart Failure: from Bidirectional Decoupling to Therapeutic Recoupling.Current heart failure reports · 2025Review
- LARP1 acts as a key mediator in preventing angiotensin II-induced cardiac dysfunction and fibrosis.Cell & bioscience · 2025Article
- DWORF Gene Therapy Improves Cardiac Calcium Handling and Mitochondrial Function.Circulation research · 2025Article
- SERCA2a dysfunction in the pathophysiology of heart failure with preserved ejection fraction: a direct role is yet to be established.Heart failure reviews · 2025Review
- LncRNA CCRR maintains CaScience China. Life sciences · 2024Article
- Impaired Cardiac AMPK (5'-Adenosine Monophosphate-Activated Protein Kinase) and CaJournal of the American Heart Association · 2024Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- Extracellular Vesicle-Encapsulated Adeno-Associated Viruses for Therapeutic Gene Delivery to the Heart.Circulation · 2023Article
- Review
- Disease modeling of desmosome-related cardiomyopathy using induced pluripotent stem cell-derived cardiomyocytes.World journal of stem cells · 2023Review
- A-Kinase Anchoring Proteins in Cardiac Myocytes and Their Roles in Regulating Calcium Cycling.Cells · 2023Review
- Cardioprotective Role for Paraoxonase-1 in Chronic Kidney Disease.Biomedicines · 2022Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Lower troponin expression in the right ventricle of rats explains interventricular differences in E-C coupling.The Journal of general physiology · 2022Article
- Mitochondrial TFAM as a Signaling Regulator between Cellular Organelles: A Perspective on Metabolic Diseases.Diabetes & metabolism journal · 2021Review
- Attenuation of the upregulation of NF‑κB and AP‑1 DNA‑binding activities induced by tunicamycin or hypoxia/reoxygenation in neonatal rat cardiomyocytes by SERCA2a overexpression.International journal of molecular medicine · 2021Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRecently, we reported that sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a), the pump responsible for reuptake of cytosolic calcium during diastole, plays a central role in the molecular mechanism of cardiac alternans. Heart failure (HF) is associated with impaired myocardial calcium handling, deficient SERCA2a, and increased susceptibility to cardiac alternans. Therefore, we hypothesized that restoring deficient SERCA2a by gene transfer will significantly reduce arrhythmogenic cardiac alternans in the failing heart. METHODS AND
resultsAdult guinea pigs were divided into 3 groups: control, HF, and HF+AAV9.SERCA2a gene transfer. HF resulted in a decrease in left ventricular fractional shortening compared with controls (P<0.001). As expected, isolated HF myocytes demonstrated slower sarcoplasmic reticulum calcium uptake, decreased Ca(2+) release, and increased diastolic Ca(2+) (P<0.05) compared with controls. Moreover, SERCA2a, cardiac ryanodine receptor 2, and sodium-calcium exchanger protein expression was decreased in HF compared with control (P<0.05). As predicted, HF increased susceptibility to cardiac alternans, as evidenced by decreased heart rate thresholds for both V(m) alternans and Ca alternans compared with controls (P<0.01). Interestingly, in vivo gene transfer of AAV9.SERCA2a in the failing heart improved left ventricular contractile function (P<0.01), suppressed cardiac alternans (P<0.01), and reduced ryanodine receptor 2 P(o) secondary to reduction of ryanodine receptor 2-P(S2814) (P<0.01). This ultimately resulted in a decreased incidence of inducible ventricular arrhythmias (P=0.05).
conclusionsThese data show that SERCA2a gene transfer in the failing heart not only improves contractile function but also directly restores electric stability through the amelioration of key arrhythmogenic substrate (ie, cardiac alternans) and triggers (ie, sarcoplasmic reticulum Ca(2+) leak).
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Registered trials
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.