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Arch Hellen Med, 26(4), July-August 2009, 439-453


Pharmacogenomics and gene therapy in heart failure

Department of Cardiothoracic Surgery, University Hospital of Patras, Rio-Patras, Greece

Heart failure is one of the most important medical states and is a major cause of morbidity and mortality in developed countries. It is not considered to be a disease itself, but the consequence of coexisting factors such as arterial hypertension, coronary heart disease and myocardiopathies. The quality of life is affected more than in any other disease and the cost of managing heart failure is high, so careful study and efforts to make patients feel better are of undoubted value. The therapeutic agents in use are numerous and are effective in curing most symptoms, but the mortality rates remain high, so new possibilities need to be studied. The role of pharmacogenomics is to find genetic variations in the genes of each patient, in order to develop new drugs suitable for the individual profile of the patient. The use of computers and special algorithms, such as differential gene expression profiling (DGE), expressed gene Databases, etc., will allow the discovery of gene targets for future therapies. Gene therapy is the technique that inserts a desirable allele into a cell, either because the cell does not have this allele or because the quantity of the produced protein is decreased. The steps that must be followed are: isolation of the target gene, development of an appropriate vector for gene transfer, identification of the target cell, in vivo gene delivery and identification of potential therapeutic targets. The targets for gene therapy are: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), superoxide dismutase (SOD), heme-oxygenase gene (HO-1) and antiapoptotic gene Bcl-2. The blockage of ╬▓ARK kinases is also studied, because it will reduce the desensitization of adrenergic action that is seen in ischemic myocardial tissue. The hope lies the future in the power of RNA interference, which is going to allow the selective degeneration of proteins that are harmful for the cell, so as to help the myocardial cell to cope with the myocardial needs.

Key words: Gene therapy, Heart failure, Pharmacogenomics.

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