INTRODUCTION: Coronary artery disease (CAD) is still the leading cause of death 
in industrialized nations. Even though revascularization strategies such as 
percutaneous coronary intervention (PCI) and coronary artery bypass graft 
surgery (CABG) as well as drug therapy have significantly reduced mortality, 
about 30% of patients will develop chronic heart failure over time. Ischemic 
heart disease and heart failure are characterized by an adverse remodeling of 
the heart, featuring cardiomyocyte hypertrophy, increased fibrosis and capillary 
rarification.
AREAS COVERED: Beside an assessment of current vector systems, this review 
focuses on potential target genes affecting angiogenesis/arteriogenesis and 
contractility. The potential of micro RNA (miRNA) modulation for the 
de-repression of survival and pro-angiogenic genes is discussed. Since gene 
therapy of the target region is preferable to avoid systemic contamination, 
application routes are discussed.
EXPERT OPINION: miRNAs are a promising new development for successful gene 
therapy, especially for acute myocardial infarction since their miRNA 
antagonists are easy to apply and appear to be selectively absorbed by the 
ischemic myocardial tissue. Rapid uptake and prolonged presence of known 
antimirs and antagomirs support this notion. For ischemic heart disease the most 
promising gene therapeutic approach seems to be the regional intravenous 
application of suitable AAV vectors and vascular growth factors, providing the 
full scope of angiogenesis, vessel maturation and collateral growth optionally 
combined with genes enhancing contractility.