Clinical & Experimental Cardiology
Open Access

Abstract

Human Interleukin-10 Naked DNA Delivery to Infarcted Pig Heart by Catheter Mediated Retrograde Injection in Coronary Sinus

Luis Sendra, Antonio Miguel, María Jose Herrero, Maria Jose Forteza, Fabian L. Chaustre, Inmaculada Noguera, Ana Diaz, Vicent Bodi and Salvador F Alino

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.