ArticleJournal of the American College of Cardiology2016
Intratracheal Gene Delivery of SERCA2a Ameliorates Chronic Post-Capillary Pulmonary Hypertension: A Large Animal Model.
Article in Journal of the American College of Cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 72 citations in OpenAlex.
- Right Ventricular Pressure-Volume Loop Analysis in Large Animal Research: A Scoping Review of Current Practices Using Conductance and Admittance Catheters.Pulmonary circulation · 2026Review
- Validation of a Göttingen Minipig Gene Therapy Biodistribution Assay for AVGN7 Using Droplet Digital Polymerase Chain Reaction.The AAPS journal · 2025Article
- A highly mobile adeno-associated virus targeting vascular smooth muscle cells for the treatment of pulmonary arterial hypertension.Nature biomedical engineering · 2025Article
- Advances and Challenges in Adeno-Associated Virus Gene Therapy Applications of Localized Delivery Strategies.Current medical science · 2025Review
- Impact of sodium-glucose cotransporter-2 inhibitors on pulmonary vascular cell function and arterial remodeling.World journal of cardiology · 2025Review
- Recent Advances in Therapeutics and Manufacturing Processes of Recombinant Adeno-Associated Virus for the Treatment of Lung Diseases.Current gene therapy · 2025Review
- State of the art and perspectives of gene therapy in heart failure. A scientific statement of the Heart Failure Association of the ESC, the ESC Council on Cardiovascular Genomics and the ESC Working Group on Myocardial & Pericardial Diseases.European journal of heart failure · 2025Review
- Aerosol Inhalation of Gene Delivery Therapy for Pulmonary Diseases.Biomolecules · 2024Review
- Endobronchial Aerosolized AAV1.SERCA2a Gene Therapy in a Pulmonary Hypertension Pig Model: Addressing the Lung Delivery Bottleneck.Human gene therapy · 2022Article
- Identifying Potential Mitochondrial Proteome Signatures Associated with the Pathogenesis of Pulmonary Arterial Hypertension in the Rat Model.Oxidative medicine and cellular longevity · 2022Article
- Preclinical models of congestive heart failure, advantages, and limitations for application in clinical practice.Frontiers in physiology · 2022Review
- Combination Therapy with STAT3 Inhibitor Enhances SERCA2a-Induced BMPR2 Expression and Inhibits Pulmonary Arterial Hypertension.International journal of molecular sciences · 2021Article
- Diagnosis and Treatment of Right Heart Failure in Pulmonary Vascular Diseases: A National Heart, Lung, and Blood Institute Workshop.Circulation. Heart failure · 2021Review
- Molecular and Genetic Profiling for Precision Medicines in Pulmonary Arterial Hypertension.Cells · 2021Review
- New Advances in Monitoring Cardiac Output in Circulatory Mechanical Assistance Devices. A Validation Study in a Porcine Model.Frontiers in physiology · 2021Article
- XPO1 Gene Therapy Attenuates Cardiac Dysfunction in Rats with Chronic Induced Myocardial Infarction.Journal of cardiovascular translational research · 2020Article
- Current and emerging therapeutic approaches to pulmonary hypertension.Reviews in cardiovascular medicine · 2020Review
- Reversal of Hypoxic Pulmonary Hypertension by Hypoxia-Inducible Overexpression of Angiotensin-(1-7) in Pulmonary Endothelial Cells.Molecular therapy. Methods & clinical development · 2020Article
- Establishment of adult right ventricle failure in ovine using a graded, animal-specific pulmonary artery constriction model.Animal models and experimental medicine · 2020Article
- Hsa_circ_0046159 is involved in the development of chronic thromboembolic pulmonary hypertension.Journal of thrombosis and thrombolysis · 2020Article
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17 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundPulmonary hypertension (PH) is characterized by pulmonary arterial remodeling that results in increased pulmonary vascular resistance, right ventricular (RV) failure, and premature death. Down-regulation of sarcoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) in the pulmonary vasculature leads to perturbations in calcium ion (Ca(2+)) homeostasis and transition of pulmonary artery smooth muscle cells to a proliferative phenotype.
objectivesWe assessed the feasibility of sustained pulmonary vascular SERCA2a gene expression using aerosolized delivery of adeno-associated virus type 1 (AAV1) in a large animal model of chronic PH and evaluated the efficacy of gene transfer regarding progression of pulmonary vascular and RV remodeling.
methodsA model of chronic post-capillary PH was created in Yorkshire swine by partial pulmonary vein banding. Development of chronic PH was confirmed hemodynamically, and animals were randomized to intratracheal administration of aerosolized AAV1 carrying the human SERCA2a gene (n = 10, AAV1.SERCA2a group) or saline (n = 10). Therapeutic efficacy was evaluated 2 months after gene delivery.
resultsTransduction efficacy after intratracheal delivery of AAV1 was confirmed by β-galactosidase detection in the distal pulmonary vasculature. Treatment with aerosolized AAV1.SERCA2a prevented disease progression as evaluated by mean pulmonary artery pressure, vascular resistance, and limited vascular remodeling quantified by histology. Therapeutic efficacy was supported further by the preservation of RV ejection fraction (p = 0.014) and improvement of the RV end-diastolic pressure-volume relationship in PH pigs treated with aerosolized AAV1.SERCA2a.
conclusionsAirway-based delivery of AAV vectors to the pulmonary arteries was feasible, efficient, and safe in a clinically relevant chronic PH model. Vascular SERCA2a overexpression resulted in beneficial effects on pulmonary arterial remodeling, with attendant improvements in pulmonary hemodynamics and RV performance, and might offer therapeutic benefit by modifying fundamental pathophysiology in pulmonary vascular diseases.
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