BMP2 gene transfer induces pericardial effusion and inflammatory response in the ischemic porcine myocardium.

Pro-angiogenic gene therapy is being developed to treat coronary artery disease (CAD). We recently showed that bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor-A synergistically regulate endothelial cell sprouting . BMP2 was also shown to induce endocardial angiogenesis in neonatal mice post-myocardial infarction.

Endocardial Gene Delivery Using NOGA Catheter System.

NOGA/MyoStar system uses low magnetic fields and endomyocardial electrical parameters, allowing precise endomyocardial injections of therapeutic agents to ischemic yet viable myocardium which is most likely to respond to the treatment. Preclinical and clinical studies have shown that NOGA/MyoStar guided intramyocardial injections are safe, feasible and a minimally invasive way to deliver gene therapy to the heart. Here we describe how to perform electroanatomical mapping and injections to hibernating myocardium in the preclinical studies.

AAV2-VEGF-B gene therapy failed to induce angiogenesis in ischemic porcine myocardium due to inflammatory responses.

Therapeutic angiogenesis induced by gene therapy is a promising approach to treat patients suffering from severe coronary artery disease. In small experimental animals, adeno-associated viruses (AAVs) have shown good transduction efficacy and long-term transgene expression in heart muscle and other tissues. However, it has been difficult to achieve cardiac-specific angiogenic effects with AAV vectors.

Adenoviral VEGF-B186R127S gene transfer induces angiogenesis and improves perfusion in ischemic heart.

Vascular endothelial growth factor B (VEGF-B) is an interesting therapeutic candidate for coronary artery disease. However, it can also cause ventricular arrhythmias, potentially preventing its use in clinics. We cloned VEGF-B isoforms with different receptor binding profiles to clarify the roles of VEGFR-1 and Nrp-1 in angiogenesis and to see if angiogenic properties can be maintained while avoiding side effects.