Human Interleukin-10 Naked DNA Delivery to Infarcted Pig Heart by Catheter Mediated Retrograde Injection in Coronary Sinus
|Luis Sendra1, Antonio Miguel1, María Jose Herrero2, Maria Jose Forteza3, Fabian L. Chaustre3, Inmaculada Noguera4, Ana Diaz4, Vicent Bodi3 and Salvador F Alino1,2,5*|
|1Department of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain|
|2Department of Pharmacogenetics, IIS La Fe, Pharmacy Service, La Fe Hospital University and Polytechnic, Valencia, Spain|
|3Department of Cardiology, University Hospital of Valencia, Valencia, Spain|
|4Service Support Center for Experimental Research (SCSIE), University of Valencia, Valencia, Spain|
|5Unit of Clinical Pharmacology, University Hospital and Polytechnic ACM La Fe, Valencia, Spain|
|Corresponding Author :||Salvador F Alino
Department of Pharmacology Faculty of Medicine
Blasco Ibanez 15, 46010, Valencia, Spain
E-mail: [email protected], [email protected]
|Received April 01, 2014; Accepted May 22, 2014; Published June 02, 2014|
|Citation: Sendra L, Miguel A, Herrero MJ, Forteza MJ, Chaustre FL, et al. (2014) Human Interleukin-10 Naked DNA Delivery to Infarcted Pig Heart by Catheter Mediated Retrograde Injection in Coronary Sinus. J Clin Exp Cardiolog 5:315. doi:10.4172/2155-9880.1000315|
|Copyright: © 2014 Sendra L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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Background: Interleukin-10 (IL-10) has proved to be important in recovery after acute myocardial infarction; increasing its expression in infarcted or bystander tissue therefore could be of great importance. Hydrodynamic DNA injection has been found to be very efficient in transferring genes to the liver of small animals, but the procedure is very aggressive and must be made compatible with clinical practice in a milder but not less efficient way. The present work evaluates the efficiency of noninvasive catheterization of the coronary sinus for human IL-10 gene transfer to infarcted and non-infarcted pig heart, with therapeutic production of the human protein.
Methods: Myocardial infarction was induced in pigs by a catheter-based approach to occlude the left anterior descending artery. After myocardial infarction verification, two catheters were placed in the coronary sinus, one of them to block blood circulation and the other to retrogradely inject 50 ml of a saline solution of DNA (20 μg/ml) containing the hIL-10 gene, and testing different flow rate conditions (control, 2, 5 and 10 ml/s).
Results: Therapeutic levels of hIL-10 protein were found in coronary sinus blood 2 and 72 hours after cathetermediated hydrofection at 5 and 10 ml/s flow rate. Molecular analyses to evaluate the delivered DNA, its transcription to RNA and translation were also performed, and data were expressed as copies per cell.
Conclusion: Catheter-mediated gene transfer through the coronary sinus is a mild and well-tolerated procedure that achieves protective hIL-10 protein levels, which could minimize the inflammatory response after myocardial infarction.