Percutaneous Cardiac Recirculation-Mediated Gene Transfer of an Inhibitory Phospholamban Peptide Reverses Advanced Heart Failure in Large Animals

• Published in: Journal of the American College of Cardiology Vol. 50; no. 3; pp. 253 - 260
• Main Authors: Kaye, David M., MD, PhD, Preovolos, Arthur, BS, Marshall, Tanneale, BS, Byrne, Melissa, PhD, Hoshijima, Masahiko, PhD, Hajjar, Roger, MD, Mariani, Justin A., MD, Pepe, Salvatore, PhD, Chien, Kenneth R., MD, PhD, Power, John M., PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 17.07.2007; Elsevier Science; Elsevier Limited
• Subjects: Adenosine triphosphatase; Animals; Biological and medical sciences; Calcium-Binding Proteins - pharmacology; Cardiology; Cardiology. Vascular system; Cardiovascular; Defects; Disease Models, Animal; Efficiency; Gene expression; Gene therapy; Gene Transfer Techniques; Genetic Therapy - methods; Genetic Vectors; Heart; Heart failure; Heart Failure - physiopathology; Heart Failure - therapy; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Internal Medicine; Medical sciences; Myocardial Revascularization - methods; Probability; Proteins; Random Allocation; Risk Assessment; Rodents; Sensitivity and Specificity; Sheep; Statistics, Nonparametric; Studies; Technological change; heart failure; Ad; LacZ; LVEF; phospholamban; SERCA; left ventricular ejection fraction; sarcoplasmic reticulum; β-galactosidase; PLN; serine-to-glutamate “pseudo-phosphorylated” phospholamban mutant; adenovirus; S16EPLN; sarcoplasmic reticulum Ca 2+-ATPase; HF; SR; Heart; Heart failure; Peptides; Cardiovascular disease; Phospholamban; Phlebology; Genetic transfer; Percutaneous route; Heart disease; Animal; Advanced stage; Circulatory system; Cardiology
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2007.03.047

Percutaneous Cardiac Recirculation-Mediated Gene Transfer of an Inhibitory Phospholamban Peptide Reverses Advanced Heart Failure in Large Animals David M. Kaye, Arthur Preovolos, Tanneale Marshall, Melissa Byrne, Masahiko Hoshijima, Roger Hajjar, Justin A. Mariani, Salvatore Pepe, Kenneth R. Chien, John M. Power The successful clinical translation of gene and cell therapy for heart failure (HF) is currently limited by the lack of safe, efficient, and selective delivery systems. We developed a novel percutaneous closed-loop recirculatory system for gene transfer in the large animal heart. In pacing-induced HF, delivery of an adenovirus expressing a pseudophosphorylated mutant of phospholamban (AdS16EPLN) significantly reversed HF progression. Hemodynamic improvements were also accompanied by significant improvement in the expression of phospholamban and Ca2+ -ATPase activity. This study documents the successful deployment of a novel closed-loop system for cardiac gene therapy in experimental HF.