Gene therapy in cardiac surgery: intramyocardial injection of naked plasmid DNA for chronic myocardial ischemia☆

Abstract

In conclusion, intramyocardial injection of naked plasmid DNA encoding VEGF(121) or FGF-2 improved myocardial function in chronic ischemia in more aspects than vector only and was superior to untreated ischemia or MCP-1. This strategy can be considered a successful tool for growth factor stimulated preservation of function in chronic myocardial ischemia.

Cardiac expression profiles of the naked DNA vectors encoding vascular endothelial growth factor and basic fibroblast growth factor

“…Approximately half of the gene therapy trials in cardiovascular field used naked DNA vectors (Isner, 2002). This can be explained in part by the relatively high transfection efficiency of naked DNA in the myocardium (Lee et al, 2000b;Isner et al, 2001;Heilmann et al, 2003). Moreover, the simplicity of DNA vector may have been an important factor in the choice of vector.…”

“…Importantly, the injected DNA vectors mostly remain episomal with greatly reduced risk for the integration into host chromosome. Also the naked DNA vectors essentially have no limit for the size of inserts and thus can accommodate larger inserts that can hardly be used effectively in other gene delivery systems (Heilmann et al, 2003). The two dominant families of angiogenic factors that have been widely studied are FGF and VEGF (Rutanen et al, 2004;Wu et al, 2004).…”

Cardiac gene therapy in large animals: bridge from bench to bedside

“…After Giordano et al 16 demonstrated successful fibroblast growth factor (FGF)-5 gene transfer and anigiogenesis in this model, many gene therapy studies targeting angiogenesis used the same model and presented positive results. Other investigators employed plastic occluders, 17 stents 18 or flow probe-adjusted stenosis 19,20 to induce gradual occlusion of an artery. Although these models are well characterized with hibernated myocardium, chronic ischemia without a significant infarction may be different from the patients who require gene therapy in the clinics.…”

“…14,[42][43][44][45][46][47][48][49][50][51][52][53][54] This form enhances collateral formation and myocardial perfusion in ameroid constrictor chronic ischemia models 46,48,50,54 as well as in coronary artery ligation ischemia models. 14,51,52 VEGF 121 gene transfer was evaluated in the chronic ischemia model, 20,55 and the pacing induced heart failure model, 26 showing improved myocardial perfusion and preserved cardiac function. Beneficial effects on myocardial perfusion were also shown in large animals using other subtypes of growth factors belonging to the VEGF family such as VEGF-B 167 , 22 VEGF-B 186 (ref.…”

“…Plasmid FGF-2 was injected intramyocardially in a pig model of left anterior descending artery stenosis resulting in improved regional contractility and perfusion. 19,20 Adenoviral gene transfer of FGF-4 (ref. 57) and FGF-5 (refs 16,17) were conducted in chronic ischemia pigs, resulting in improved blood flow and cardiac function.…”