From Gene to Epigene-Based Therapies Targeting the Vascular Endothelium

Adam      J. Lewandowski; Esther      F. Davis; Merzaka      Lazdam; Paul      Leeson

Abstract

Vascular endothelial dysfunction is a key biological process underlying the development of cardiovascular disease and therefore of potential importance as a target for gene-based therapy. Modification of nitric oxide bioavailability through gene therapy is possible in animal studies and of clinical relevance because of the central role for nitric oxide in vascular homeostasis. However, most clinical trials have so far focused on endothelial-related pathways, in particular, vascular endothelial growth factor, to induce angiogenesis, with variable results. The slow progress of the development of gene-therapy targeted at the endothelium relates to a range of complexities of design of therapy including mode of gene delivery. This is usually achieved through the use of viral or non-viral vectors but the best physical and vector methods for delivery of complimentary DNA to the vascular endothelium remains under investigation. More recently there has been emerging interest into other genome-based methods to alter vascular phenotype, in particular, gene-based modification of endothelial progenitor cell function and whether gene function might be modifiable through induced epigenetic changes.

Keywords: Genetics, atherosclerosis, vascular endothelium, epigene therapies, endothelial dysfunction, cardiovascular disease, vascular homeostasis, diabetes, hypertension, non-viral vectors