Project

Effect of Sesquiterpenes on Vascular Smooth Muscle and Vascular Endothelial Cell Proliferation, Migration and Viability


Supervisor(s)

Dr Paul Coats

Area

Description

Myocardial infarction, stroke and peripheral vascular disease are all driven by vascular occlusive disease. Endothelial dysfunction and vascular hyper-proliferative remodelling are the hallmark of atherosclerosis, re-stenosis and hypertensive vascular disease associated with vascular occlusive disease. Bypass grafting, balloon angioplasty and drug eluting stent insertion are the interventions of choice to treat vascular occlusive disease. However these options are associated with numerous problems as a consequence on the complex nature of disease pathology and the limited efficacy of the drugs used to treat the condition. We have generated significant pilot data highlighting sesquiterpenes isolated from natural products demonstrate significant vascular smooth muscle (VSM) cells anti-inflammatory and anti-mitogenic properties yet are not toxic to endothelial cells. As such sesquiterpenes may offer very significant advantages over existing used compounds which are endothelial toxic. This project will study the effect of isolated sesquiterpenes on VSM cell proliferation, migration and toxicology (apoptosis, necrosis and autophagy assays).  Similar will be undertaken in vascular endothelial cells. The project will ultimately progress to co-culture (endothelial and VSM cells) and intact blood vessel culture work to determine optimal sesquiterpenes candidates for use in novel drug delivery systems.

Project Aim: Using cell proliferation, migration and toxicology studies (apoptosis, necrosis and autophagy assays) this project will investigate the novel use of sesquiterpenes as candidates for novel drug delivery systems used for vascular disease.  

Techniques

The project mainly involves cell tissue culture. Western blotting; proliferation assays, migration assays, ELISA, Immunofluorescent microscopy

References

  1. Nikam N, Steinberg TB, Steinberg DH. Advances in stent technologies and their effect on clinical efficacy and safety. Med Devices (Auckl). 2014, 3; 7: 165-78. http://www.ncbi.nlm.nih.gov/pubmed/2494008
  2. Pendyala L, Jabara R, Shinke T, Chronos N, Robinson K, Li J, Hou D. Drug-eluting stents: present and future. Cardiovasc Hematol Agents Med Chem. 2008; 6: 105-15. http://www.ncbi.nlm.nih.gov/pubmed/18473775
  3. Sakakura K, Nakano M, Otsuka F, Ladich E, Kolodgie FD, Virmani R. Pathophysiology of atherosclerosis plaque progression. Heart Lung Circ. 2013; 22: 399-411.  http://www.ncbi.nlm.nih.gov/pubmed/23541627