This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease.
Recent experiments performed in this same porcine model of myocardial ischemia have shown that direct intramyocardial gene transfer of naked plasmid DNA encoding VEGF (phVEGF(165), the identical plasmid used in our previous animal and human clinical trials) can be safely and successfully achieved through a minimally invasive chest wall incision.
We correlated the VEGF response to hypoxia in the monocytes harvested from patients with coronary artery disease with the presence of collaterals visualized during routine angiography.
We initiated a phase 1 clinical study to determine the safety and bioactivity of direct myocardial gene transfer of vascular endothelial growth factor (VEGF) as sole therapy for patients with symptomatic myocardial ischemia.
In this brief review, the role of a prime angiogenic candidate, namely vascular endothelial growth factor (VEGF) and its homologues, in physiological and pathological angiogenesis will be discussed with particular attention to myocardial ischemia and heart failure.
Recently, the efficacy of therapeutic angiogenesis using VEGF (vascular endothelial growth factor) gene transfer has been reported in human patients with critical limb ischemia and myocardial ischemia.
3 years) with chronic stable angina due to angiographically documented coronary artery disease, all of whom had failed conventional therapy (drugs, PTCA, and/or CABG), were treated with direct myocardial injection of phVEGF(165) via a minithoracotomy.
Several clinical trials based on intramyocardial injection of VEGF DNA in patients with otherwise inoperable coronary artery disease and intractable angina pectoris have recently been completed.
The central role of vascular endothelial growth factor (VEGF) in angiogenesis in health and disease makes it attractive both as a therapeutic target for anti-angiogenic drugs and as a pro-angiogenic cytokine for the treatment of ischaemic heart disease.
The results of application of vascular endothelial growth factor (VEGF) GT strategies for therapeutic angiogenesis in critical limb and myocardial ischemia in pilot clinical trials was reviewed.
Direct intramyocardial administration of VEGF(165)-DNA and VEGF(167)-DNA may result occasionally in an enhancement of collateral vascularization in regions with diffuse peripheral coronary artery disease not surgically amenable.
Currently, about 200 patients have been treated with intramyocardial VEGF gene therapy for peripheral occlusive artery disease or for myocardial ischemia.
However, more research including large scaled clinical trials is needed before deciding whether the vascular endothelial growth factor therapy either as a gene or a recombinant slow-release protein formulation therapy can be offered to patients with severe coronary artery disease, which cannot be treated with conventional revascularization.
Because hypoxia-inducible factor (HIF)-1alpha is a transcriptional activator of vascular endothelial growth factor (VEGF) and is critical for initiating angiogenic responses to hypoxia, we investigated the expression of HIF-1alpha and VEGF in specimens of human heart tissue to elucidate the molecular responses to myocardial ischemia in diabetic patients during unstable angina.
Mobilization of endothelial progenitor cells with cytokines potentiates VEGF-2 gene therapy for myocardial ischemia and enhances bone marrow cell incorporation into ischemic myocardium.