Gene Therapeutic Approaches to Oxidative Stress-Induced Cardiac Disease: Principles,Progress,and Prospects

Heart and vascular diseases continue to rank among the most frequent and devastating disorders to affect adults in many parts of the world. Increasing evidence from a variety of experimental models indicates that reactive oxygen species can play a key role in the development of myocardial damage from ischemia/reperfusion, the development of cardiac hypertrophy, and the transition of hypertrophy to cardiac failure. The recent dramatic increase in availability of genomic data has included information on the genetic modulation of reactive oxygen species and the antioxidant systems that normally prevent damage from these radicals. Nearly simultaneously, progressively more sophisticated and powerful methods for altering the genetic complement of selected tissues and cells have permitted application of gene therapeutic methods to understand better the pathophysiology of reactive oxygen species-mediated myocardial damage and to attenuate or treat that damage. Although exciting and promising, gene therapy approaches to these common disorders are still in the experimental and developmental stages. Improved understanding of pathophysiology, better gene delivery systems, and specific gene therapeutic strategies will be needed before gene therapy of oxyradical-mediated myocardial damage becomes a clinical reality.