935. Restoration of Impaired Myocardial Contractility by Overexpressing Sarcoplasmic Reticulum Calcium ATPase through Recombinant Adeno-Associated

• Published in: Molecular therapy Vol. 11; no. S1; p. S362
• Main Authors: Lu, Xiaochun, Hui, Haipeng, Li, Xiaoying, Wu, Xiaobing
• Format: Journal Article
• Language: English
• Published: Milwaukee Elsevier Inc 01-05-2005; Elsevier Limited
• Subjects: Angioplasty; Antigens; Atherosclerosis; Carotid arteries; Cytotoxicity; Dendritic cells; Endothelium; Gene therapy; Heart failure; Hemodynamics; Rabbits; Smooth muscle; Vectors (Biology); Veins & arteries; New Zealand; Beijing China; China
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2005.07.478

Objective: Congestive heart failure is the syndrome of final stage in most heart diseases, which prognosis is worst. Alterations of calcium-regulatory are the certain access, whereas Function and regulation of sarcoplasmic reticulim Ca2+ -ATPase are the definitive factors to maintain the calcium equilibrium in cardiomyocyts, and abnormalities of calcium cycling in the failing heart. To assess value in the gene therapy of congestive heart failure, A recombinant Adeno-Associated Virus, which delivery the express of SERCA2a in cardiomyocyts, was constructed and employed in animal experiment.Methods: A recombinant Adeno-Associated Virus, named rAAV-SERCA2a, was constructed according to the strategy "a recombinant helper virus infecting a carrier cell, in which the SERCA2a cDNA was inserted under the control of CMV promoter. RT-PCR was performed to analysis SERCA2a expression in BHK-21 cell infected with rAAV-SERCA2a. Abdominal aortic coarctation rat model that aortery coarctated diameter 0.7mm just above double renal arteris were prepared, rat caudal artery press measure and M-mode echocardiograph were performed to evaluate the heart function. After heart failure affirmed, the rAAV were injected into pericardial cavity through diaphragm. The hemodynamics parameters were record by left ventricle ar terial cannulation through carotid artery 10 and 30 days after rAAV injected.Results: We produced the recombinant adeno-associated virus rAAV-SERCA2a which titre was 2×10 12 v.g./ml and could effectively mediate SERCA2a expression. It turn up the aortery coarctation success that rat caudal artery press measure was zero.The l eft ventricle of aortery coarctation group was more hypertrothied than that of control group 12 weeks after coarctation operation. The left ventricle was bigger with heart constraction function reduced, LVEDP increased, tachycardia and FS<45% in aortery coarctation groups, which indicate heart failure. The hemodynamics state of rAAV-SERCA2a group was better than that of control and rAAV2-EGFP group in 10 days and 30days after virus delivery, the LVSP, +dp/dt and -dp/dt were improved 56.5%,109.8% and 99.8%, meanwhile the LVEDP lower 60.3% than rAAV2-EGFP group in 30days after virus delivery.Conclusion: This recombinant adeno-associated virus, rAAV-SERCA2a effectively delivery the SERCA2a gene. This product injected aortic coarctation rat can improve the hemodynamics state of heart failure rats.