Molecular and cell-based therapies for protection, rescue, and repair of ischemic myocardium: reasons for cautious optimism.

Despite the significant therapeutic advances of the past 25 years, coronary ischemic artery disease (CAD) remains the predominant cause of premature death.1,2 The prevalence of the disease imposes enormous financial strain on the healthcare system,2,3 calling for new approaches for treatment of CAD. The availability of cardiotropic vectors capable of long-term and stable protein expression4 and the recent isolation of progenitor cells with regenerative and angiogenic potential5,6 may provide opportunities for the design of novel therapies for protection and rescue of the myocardium from ischemia and failure. Cardioprotective gene therapy strategies have been effective in animal models of myocardial ischemia and reperfusion injury,7,8 and gene transfer of proangiogenic cytokines has been used as a strategy for rescuing ischemic myocardium.9 Transplantation of autologous progenitor cells is emerging as a potential option for the revascularization and repair of ischemic and infarcted myocardium.6 Notwithstanding these promising findings, there is pressing need for the development of safer and more effective vectors and the optimization and standardization of gene- and cell-based therapies. In this article, we discuss the current preclinical and clinical advances in gene- and cell-based therapies for protection, rescue, and repair of the ischemic myocardium, with emphasis on strategies for protection of the myocardium from ischemia and reperfusion injury and for neovascularization and regeneration of ischemic and infarcted myocardium. The development of gene therapies for acute myocardial infarction (MI) is not possible with the current vectors because the time required for transcription and translation of therapeutic genes exceeds the time window for successful intervention. For this reason, gene transfer of anticoagulant genes is not feasible as primary thrombolytic therapy for acute MI. Alternatively, a gene therapy strategy may be devised to provide long-term myocardial protection from ischemia-induced injury. This novel preventive gene therapy concept would protect …

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