Progress in Gene Therapy for Chronic Heart Failure

Abstract

Chronic heart failure (CHF) is still the leading cause of morbidity and mortality worldwide, and carries with it large economic and social burdens. Although steady and substantial progress has been made in reducing mortality from heart failure using conventional treatments, novel pharmacologic and surgical interventions have not been effective in extending five year survival rates. Therefore, it is necessary to explore new therapies. Gene therapy was introduced in 1970s with the development of recombinant DNA technology. Due to recent progress in the understanding of myocardial metabolism and application of vector based gene transfer strategies in animal models and initial clinical trials, gene therapy possibly affords an ideal treatment alternative for CHF. In last 2 decades, much research has been done on gene therapy, using various genes, signal transduction passages and delivery methods to treat advanced heart failure. Current research in ischemic heart disease (IHD) mainly focuses on stimulating angiogenesis, modifying the coronary vascular environment, and improving the vascular endothelial function with localized gene coated catheters and stents. Compared with standard ischemic heart disease treatment, the main goal of gene therapy for CHF is to inhibit apoptosis, reduce the undesirable remodeling and increase contractility through the most efficient cardiomyocyte transfection [Katz 2012a]. In this paper, we review various gene transfer technologies in ischemic heart disease and heart failure models, and discuss the advantages and disadvantages of these strategies in vector-mediated cardiac gene delivery, with the main focus on the high efficiency approach of a molecular cardiac surgery delivery system.