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Targeting ischemic cardiac dysfunction through gene transfer
Takashi Matsui1, Anthony Rosenzweig
1Program in Cardiovascular Gene Therapy, Massachusetts General Hospital, 114 16th Street, Room 2600, Charlestown, MA 02129, USA. arosenzweig@partners.org
Insights
Apoptotic cardiomyocyte death contributes to ischemic cardiac injury from atherosclerosis. Targeting survival pathways offers potential therapeutic strategies for ischemic heart disease.
Area of Science:
- Cardiovascular Biology
- Cellular Biology
- Pathophysiology
Background:
- Atherosclerosis is a leading cause of global morbidity and mortality.
- Ischemic cardiac injury is a significant complication of atherosclerosis.
- Apoptotic cardiomyocyte death's role in ischemic injury is not fully understood.
Purpose of the Study:
- To review general mechanisms of apoptosis.
- To present evidence on the functional contribution of apoptotic cell death in ischemic injury.
- To identify potential therapeutic targets for ischemic heart disease.
Main Methods:
- Review of general apoptosis mechanisms.
- Analysis of interventional studies on ischemic injury.
- Discussion of gene transfer as a research and therapeutic tool.
Main Results:
- Apoptotic cell death plays a significant role in the pathogenesis of ischemic injury.
- Signaling pathways regulating cardiomyocyte survival and function converge.
- These converging pathways are attractive therapeutic targets.
Conclusions:
- Apoptotic cardiomyocyte death is functionally important in ischemic heart disease.
- Targeting converging survival pathways holds therapeutic promise.
- Gene transfer is a valuable tool for target validation and therapy.
Abstract:
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.