Simultaneous surgical revascularization and angiogenic gene therapy in diffuse coronary artery disease

Abstract

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. During midterm follow-up no adverse effects of VEGF-DNA application are observed so far. The very slight midterm improvements caused us to stop further VEGF-DNA application and, in our opinion, do not justify a prospective, and randomized study with a control group.

Therapeutic angiogenesis using naked DNA expressing two isoforms of the hepatocyte growth factor in a porcine acute myocardial infarction model☆

“…Vascular endothelial growth factor (VEGF) has been studied in ischemic heart disease. Although it demonstrated increased myocardial perfusion in various clinical trials, VEGF failed to meet the goal of therapeutic angiogenesis, consistent myocardial functional improvement [2,3]. Recently, hepatocyte growth factor (HGF), initially purified and cloned as a potent mitogen of hepatocytes [4], has increasingly been used due to its potent mitogenic, motogenic, angiogenic, and anti-apoptotic effects in various cell types after binding of the membrane tyrosine kinase receptor encoded by c-met proto-oncogene [5].…”

Efficacy of Sirolimus Eluting Stents Implantation in Diffuse (Long and Extremely Long) Coronary Atherosclerotic Lesions

“…предложена операция лазерной туннелизации мио-карда, однако, несмотря на вполне обнадеживающие первые клинические результаты [12][13][14], эта операция так и не смогла стать массовой при указанном типе атеросклеротических поражений коронарных арте-рий [15,16]. Другие методы, такие как in-situ артери-ализация венозной системы сердца из-за плохого состояния дистального русла [17], сочетание хирурги-ческой реваскуляризации с генной терапией (интра-коронарное введение фактора роста эндотелиальных клеток VEGF) [18] пока находятся на стадии разра-ботки. Интервенционные методы лечения до послед-него времени считались малоэффективными.…”

Gene therapy progress and prospects: therapeutic angiogenesis for limb and myocardial ischemia

“…37 Although these results as a whole suggest the therapeutic efficacy of angiogenesis by gene transfer, a study of intramyocardial gene transfer of plasmid DNA encoding VEGF-A and VEGF-B as an adjunct to CABG in 24 patients was published recently that provided only modest evidence of improved perfusion. 38 The angiogenic gene therapy (AGENT) study was the first randomized, double-blind, placebo-controlled trial of therapeutic angiogenesis by gene transfer for myocardial ischemia. FGF-4 carried by an adenoviral vector was given intracoronary to 79 patients with chronic stable angina randomized in a 1:3 ratio to produce 19 in the control group and 60 in the treatment group.…”