Role of periodontitis on macrophage polarisation and subsequent association in cardiovascular disease
Periodontitis is associated with an increased risk of atherosclerosis which leads to coronary artery disease and death (1). A wealth of clinical and epidemiological data substantiates a central role of inflammation in atherosclerosis. The macrophage plays a central role (2). They are a major source of pro-inflammatory cytokines and are implicated in the earliest events of plaque initiation as well as later stages of progression. Triggered by initial endothelial dysfunction, monocytes influx into the intima where they differentiate into macrophages and take up modified lipids to become foam cells. The continued inflammatory response leads to plaque formation, enhanced by impairment of apoptotic macrophage clearance; contributing to plaque instability and subsequent rupture.
Macrophages polarise into different subsets and these have been identified in animal models and human samples (3). This PhD will focus on macrophage polarisation in periodontitis and coronary artery disease. It will exploit monocyte/macrophage samples from patients with periodontitis and coronary disease and tease out the potentially mechanisms underlying enhanced coronary artery disease in periodontitis patients. We will also determine whether exposure to different bacterial strains affects polarisation.
The hypothesis for this PhD is:
Compared to the general population periodontitis patients show greater polarisation of monocyte/macrophage towards a pro-atherogenic, inflammatory phenotype due to exposure to periodontal bacteria.
For this PhD, the student will undertake in vitro experiments on samples obtained from the following patients and healthy volunteers. They will gain valuable experience in a number of techniques including cell culture, flow cytometry, immunocytochemistry, Q-PCR, Western blotting and histology.
When applying please select ’Medicine PhD’ within the Faculty of Health Sciences.