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Gene therapy in heart failure Vinge LE; Raake PW; Koch WJCirc Res 2008[Jun]; 102 (12): 1458-70With increasing knowledge of basic molecular mechanisms governing the development of heart failure (HF), the possibility of specifically targeting key pathological players is evolving. Technology allowing for efficient in vivo transduction of myocardial tissue with long-term expression of a transgene enables translation of basic mechanistic knowledge into potential gene therapy approaches. Gene therapy in HF is in its infancy clinically with the predominant amount of experience being from animal models. Nevertheless, this challenging and promising field is gaining momentum as recent preclinical studies in larger animals have been carried out and, importantly, there are 2 newly initiated phase I clinical trials for HF gene therapy. To put it simply, 2 parameters are needed for achieving success with HF gene therapy: (1) clearly identified detrimental/beneficial molecular targets; and (2) the means to manipulate these targets at a molecular level in a sufficient number of cardiac cells. However, several obstacles do exist on our way to efficient and safe gene transfer to human myocardium. Some of these obstacles are discussed in this review; however, it primarily focuses on the molecular target systems that have been subjected to intense investigation over the last decade in an attempt to make gene therapy for human HF a reality.|*Genetic Therapy/adverse effects/methods[MESH]|Adenylyl Cyclases/genetics/physiology[MESH]|Animals[MESH]|Animals, Genetically Modified[MESH]|Calcium Signaling/drug effects/genetics[MESH]|Calcium-Binding Proteins/antagonists & inhibitors/genetics/physiology[MESH]|Clinical Trials, Phase I as Topic[MESH]|Cricetinae[MESH]|G-Protein-Coupled Receptor Kinase 2/antagonists & inhibitors[MESH]|Genetic Vectors/administration & dosage/therapeutic use[MESH]|Heart Failure/drug therapy/genetics/physiopathology/*therapy[MESH]|Humans[MESH]|Mice[MESH]|Myocytes, Cardiac/physiology[MESH]|Organ Specificity[MESH]|Parvalbumins/genetics/physiology[MESH]|Protein Phosphatase 1/physiology[MESH]|Rabbits[MESH]|Rats[MESH]|Receptors, Adrenergic, beta/classification/genetics/physiology[MESH]|S100 Proteins/genetics/physiology[MESH]|Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics/physiology[MESH] |
