ArticleScience translational medicine2011
Cardiac AAV9-S100A1 gene therapy rescues post-ischemic heart failure in a preclinical large animal model.
Article in Science translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 2 of them syntheses that pooled it.
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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
128 citing papers in PubMed, 2 syntheses or guidelines pooled it, 231 citations in OpenAlex.
- Progress in the treatment of diabetic cardiomyopathy, a systematic review.Pharmacology research & perspectives · 2024Pooled it
- Pathophysiological mechanism and therapeutic role of S100 proteins in cardiac failure: a systematic review.Heart failure reviews · 2016Pooled it
- Nrf2 de-SUMOylation alleviates myocardial ischemia-reperfusion injury (MIRI) by attenuating myocardial ferroptosis in mice.Redox report : communications in free radical research · 2026Article
- Adeno-Associated Virus Vector Mediated Gene Therapy: A Promising Approach to Transform Hypertrophic Cardiomyopathy Treatment.Biotechnology journal · 2026Review
- Gene Therapy for Heart Failure.Journal of cardiovascular translational research · 2026Review
- Gene Therapy for Heart Failure: Impact on Mitochondrial Dysfunction.Biomedicines · 2026Review
- Calcium dysregulation in diabetic cardiomyopathy & heart failure with preserved ejection fraction.Frontiers in cardiovascular medicine · 2026Review
- Cardiac gene therapy makes a comeback.Nature medicine · 2025Article
- Validation of a Göttingen Minipig Gene Therapy Biodistribution Assay for AVGN7 Using Droplet Digital Polymerase Chain Reaction.The AAPS journal · 2025Article
- Novel therapeutic cav1.3-C-terminus normalizes L-type calcium current and ejection fraction in ischemia-induced murine heart failure.Biochemical and biophysical research communications · 2025Article
- AAV6 vectors provide superior gene transfer compared to AAV9 vectors following intramyocardial administration.Molecular therapy. Methods & clinical development · 2025Article
- Cardiac-Targeted AAV5-S100A1 Gene Therapy Protects Against Adverse Remodeling and Contractile Dysfunction in Postischemic Hearts.Circulation. Heart failure · 2025Article
- Evaluation of AAV vectors with tissue-specific or ubiquitous promoters in a mouse model of mucopolysaccharidosis type IVA.Molecular therapy. Methods & clinical development · 2025Article
- Transcriptomic Signature of Frailty in Older Patients With Cardiovascular Disease Undergoing Cardiac Surgery or TAVI.Journal of cachexia, sarcopenia and muscle · 2025Article
- Cardiac remodelling in the era of the recommended four pillars heart failure medical therapy.ESC heart failure · 2025Review
- S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models.Circulation · 2025Article
- AAV viral vectors as therapeutic interventions for inherited or non-inherited cardiac disorders: current aspects and future prospects.Frontiers in medicine · 2025Review
- CITED4 gene therapy protects against maladaptive cardiac remodeling after ischemia/reperfusion injury in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Structural insights into the regulation of RyR1 by S100A1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Extracellular Vesicle-Encapsulated Adeno-Associated Viruses for Therapeutic Gene Delivery to the Heart.Circulation · 2023Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
As a prerequisite for clinical application, we determined the long-term therapeutic effectiveness and safety of adeno-associated virus (AAV)-S100A1 gene therapy in a preclinical large animal model of heart failure. S100A1, a positive inotropic regulator of myocardial contractility, becomes depleted in failing cardiomyocytes in humans and animals, and myocardial-targeted S100A1 gene transfer rescues cardiac contractile function by restoring sarcoplasmic reticulum calcium (Ca(2+)) handling in acutely and chronically failing hearts in small animal models. We induced heart failure in domestic pigs by balloon occlusion of the left circumflex coronary artery, resulting in myocardial infarction. After 2 weeks, when the pigs displayed significant left ventricular contractile dysfunction, we administered, by retrograde coronary venous delivery, AAV serotype 9 (AAV9)-S100A1 to the left ventricular, non-infarcted myocardium. AAV9-luciferase and saline treatment served as control. At 14 weeks, both control groups showed significantly decreased myocardial S100A1 protein expression along with progressive deterioration of cardiac performance and left ventricular remodeling. AAV9-S100A1 treatment prevented and reversed these functional and structural changes by restoring cardiac S100A1 protein levels. S100A1 treatment normalized cardiomyocyte Ca(2+) cycling, sarcoplasmic reticulum calcium handling, and energy homeostasis. Transgene expression was restricted to cardiac tissue, and extracardiac organ function was uncompromised. This translational study shows the preclinical feasibility of long-term therapeutic effectiveness of and a favorable safety profile for cardiac AAV9-S100A1 gene therapy in a preclinical model of heart failure. Our results present a strong rationale for a clinical trial of S100A1 gene therapy for human heart failure that could potentially complement current strategies to treat end-stage heart failure.
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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.