Occlusive atherosclerotic peripheral arterial disease (PAD) is a significant cause of patient morbidity and mortality in the community, particularly in the growing diabetic population, susceptible to an accelerated form of this condition. Balloon angioplasty, intra-arterial stent insertion and bypass graft surgery are used for the successful treatment of symptomatic PAD although a significant percentage of these procedures fail due to vessel and/or graft re-occlusion secondary to injury induced neointimal hyperplasia (NIH). In attempts to reduce NIH stents and angioplasty balloons have been coated with anti-proliferative agents. Drug eluting balloon (DEB) angioplasty devices have recently been demonstrated to be superior to drug eluting stents. Paclitaxel coated DEB's are the only currently available DEB's and concerns have been raised regarding potential vascular and systemic toxicity and thrombosis associated with use of paclitaxel DEB's. Epigenetic regulation of gene expression via inhibition of histone deacetylation affords one potential mechanism for attenuation of NIH post vascular intervention. We have synthesized a novel histone deacetylase inhibitor (HDACi) MCT-3, and demonstrated significant anti-NIH activity utilising prototype MCT-3 coated DEB's, termed "Epi-solve", in a large animal model. Our aim is to confirm efficacy of Epi-solve DEB's in a large animal model of NIH and compare this, and toxicity profiles, to paclitaxel DEB's. The basis of our proposal is the development and evaluation of a novel angioplasty DEB device.
Epigenetic, restenosis, vascular disease, angioplasty
Eastern Health Clinical School
Top-up scholarship funding available
Eastern Health Clinical School and ACBD, AMREP Facility (<10%)
Hong Bin Liu