Targeting ischemic cardiac dysfunction through gene transfer.
Ischemic cardiac injury is a complication of atherosclerosis, which remains a major contributor to morbidity and mortality throughout much of the world. Previous studies have documented apoptotic cardiomyocyte death in this setting; however, its functional contribution remains incompletely defined. We briefly review general mechanisms of apoptosis and then present evidence from interventional studies that suggests apoptotic cell death may indeed play an important role in the pathogenesis of ischemic injury. In some instances, the signaling pathways controlling both cardiomyocyte survival and function appear to converge, suggesting these pathways may represent particularly attractive targets for therapeutic intervention in ischemic heart disease. In this context, gene transfer provides both a powerful experimental tool for validating such targets for intervention, as well as an approach to therapy.
Matsui
Takashi
T
Program in Cardiovascular Gene Therapy, Massachusetts General Hospital, 114 16th Street, Room 2600, Charlestown, MA 02129, USA. arosenzweig@partners.org
Rosenzweig
Anthony
A
D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D006801:Humans; D017202:Myocardial Ischemia / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D032383:Myocytes, Cardiac / Q000502:physiology