Angiogenic gene therapy in cardiovascular diseases: dream or vision?

Abstract

Chronic cardiovascular diseases are significant health problems. Although current treatment strategies have tremendously improved disease management, up to 30% of these patients cannot be successfully treated with current treatment approaches and new treatment strategies are clearly needed. Gene therapy and therapeutic vascular growth may provide a new treatment option for these patients. Several growth factors, like vascular endothelial growth factors, fibroblast growth factors and hepatocyte growth factor have been tested in clinical trials. However, apart from demonstration of increased vascularity, very few results with clinical significance have been obtained. Problems with gene transfer efficiency, short duration of transgene expression, selection of endpoints, and suboptimal patients for gene therapy have been recognized. Ongoing gene therapy trials have included improvements in study protocols, vector delivery and endpoints, addressing the identified problems. Better, targeted delivery systems and new, more optimal growth factors have been taken to clinical testing. Recent advances in these areas will be discussed and the concept of angiogenic therapy as a sole treatment is re-evaluated. A combination with regenerative therapies or standard revascularization operations might be needed to improve tissue function and clinical benefits.

Local adventitial anti-angiogenic gene therapy reduces growth of vasa-vasorum and in-stent restenosis in WHHL rabbits

“…Treatment with AdsVEGFR1 and AdsVEGFR2 resulted in an attenuated adventitial angiogenic response two weeks after the treatment, following the peak transgene expression of adenovirus vector system [26]. Possibly due to the limited duration of expression of adenoviruses, the effect on the vasa vasorum size and density was lost at the later time points.…”

Biomaterial Based Strategies for Engineering New Lymphatic Vasculature

“…One solution involves delivering gene therapies, which can provide continuous expression of therapeutics at a specifically targeted cell type or tissue to promote revascularization. [205] An appealing gene therapy strategy involves direct gene delivery in vivo. [206] This direct approach avoids the technical challenges with ex vivo manipulation, but at the loss of control over cell targeting and dosages.…”

The TRPC5 channel regulates angiogenesis and promotes recovery from ischemic injury in mice

“…Effective treatment options for ischemia-hypoxia-related diseases are limited. Although targeting angiogenic factors, such as VEGF, is an attractive strategy, and VEGF has shown optimistic results in the laboratory, clinical trial results of angiogenic cytokines for ischemic disease therapy are controversial and inconclusive (5,10,14,15,35,36). In one study, adVEGF121 was delivered intramuscularly to the lower legs of patients with peripheral arterial disease.…”

“…Although traditional surgical bypass treatment along with medical therapy show better efficacy than medical therapy alone, and endovascular intervention is associated with decreased periprocedural morbidity and mortality, the therapeutic effects are still limited, including high risk of restenosis, unknown durability, and so on (7)(8)(9). Therapeutic angiogenesis to promote blood flow is therefore key when treating ischemia-related diseases (4,5,10).…”