ArticleThe Journal of thoracic and cardiovascular surgery2014
Safety and efficacy of high-dose adeno-associated virus 9 encoding sarcoplasmic reticulum Ca(2+) adenosine triphosphatase delivered by molecular cardiac surgery with recirculating delivery in ovine ischemic cardiomyopathy.
Article in The Journal of thoracic and cardiovascular surgery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Gene Therapy for Heart Failure: Impact on Mitochondrial Dysfunction.Biomedicines · 2026Review
- AAV6 vectors provide superior gene transfer compared to AAV9 vectors following intramyocardial administration.Molecular therapy. Methods & clinical development · 2025Article
- Adeno-Associated Viral Transfer of Glyoxalase-1 Blunts Carbonyl and Oxidative Stresses in Hearts of Type 1 Diabetic Rats.Antioxidants (Basel, Switzerland) · 2020Article
- Effects of genetic transfection on calcium cycling pathways mediated by double-stranded adeno-associated virus in postinfarction remodeling.The Journal of thoracic and cardiovascular surgery · 2020Article
- Primary Effect of SERCA 2a Gene Transfer on Conduction Reserve in Chronic Myocardial Infarction.Journal of the American Heart Association · 2018Article
- Technique of Complete Heart Isolation with Continuous Cardiac Perfusion During Cardiopulmonary Bypass: New Opportunities for Gene Therapy.The journal of extra-corporeal technology · 2018Article
- Correcting Calcium Dysregulation in Chronic Heart Failure Using SERCA2a Gene Therapy.International journal of molecular sciences · 2018Review
- The Gene Therapy Resource Program: A Decade of Dedication to Translational Research by the National Heart, Lung, and Blood Institute.Human gene therapy. Clinical development · 2017Article
- Promise of adeno-associated virus as a gene therapy vector for cardiovascular diseases.Heart failure reviews · 2017Review
- Use of Adeno-Associated Virus Vector for Cardiac Gene Delivery in Large-Animal Surgical Models of Heart Failure.Human gene therapy. Clinical development · 2017Review
- Cardiac gene therapy with adeno-associated virus-based vectors.Current opinion in cardiology · 2017Article
- Article
- Cardiac gene therapy: are we there yet?Gene therapy · 2016Review
- The Role of p38 MAPK in the Development of Diabetic Cardiomyopathy.International journal of molecular sciences · 2016Review
- Gene Therapy in Cardiac Surgery: Clinical Trials, Challenges, and Perspectives.The Annals of thoracic surgery · 2016Review
- Mitigation of myocardial fibrosis by molecular cardiac surgery-mediated gene overexpression.The Journal of thoracic and cardiovascular surgery · 2016Article
- Ribonucleotide reductase-mediated increase in dATP improves cardiac performance via myosin activation in a large animal model of heart failure.European journal of heart failure · 2015Article
- Adeno-associated virus-mediated gene therapy in cardiovascular disease.Current opinion in cardiology · 2015Review
- Characterizing preclinical model of ischemic heart failure: difference between LAD and LCx infarctions.American journal of physiology. Heart and circulatory physiology · 2015Article
- Stimulating endogenous cardiac repair.Frontiers in cell and developmental biology · 2015Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveTherapeutic safety and efficacy are the basic prerequisites for clinical gene therapy. We investigated the effect of high-dose molecular cardiac surgery with recirculating delivery (MCARD)-mediated adeno-associated virus 9 (AAV9)/sarcoplasmic reticulum Ca(2+) adenosine triphosphatase (SERCA2a) gene delivery on clinical parameters, oxidative stress, humoral and cellular immune responses, and cardiac remodeling.
methodsIschemic cardiomyopathy was generated in a sheep model. The sheep were assigned to 1 of 2 groups: control (n = 10) and study (MCARD, n = 6). The control group underwent no intervention and the study group received 10(14) genome copies of AAV9/SERCA2a 4 weeks after infarction.
resultsOur ischemic model produced reliable infarcts leading to heart failure. The baseline ejection fraction in the MCARD group was 57.6% ± 1.6% versus 61.2% ± 1.9% in the control group (P > .05). At 12 weeks after infarction, the MCARD group had superior left ventricular function compared with the control group: stroke volume index, 46.6 ± 1.8 versus 35.8 ± 2.5 mL/m(2) (P < .05); ejection fraction, 46.2% ± 1.9% versus 38.7% ± 2.5% (P < .05); and left ventricular end-systolic and end-diastolic dimensions, 41.3 ± 1.7 versus 48.2 ± 1.4 mm and 51.2 ± 1.5 versus 57.6 ± 1.7 mm, respectively (P < .05). The markers of oxidative stress were significantly reduced in the infarct zone in the MCARD group. No positive T-cell-mediated immune response was seen in the MCARD group at any point. Myocyte hypertrophy was also significantly attenuated in the MCARD group compared with the control group.
conclusionsCardiac overexpression of the SERCA2a gene by way of MCARD is a safe therapeutic intervention. It significantly improves left ventricular function, decreases markers of oxidative stress, abrogates myocyte hypertrophy, arrests remodeling, and does not induce a T-cell-mediated immune response.
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