Cardiovascular disease (CVD) is the leading cause of death in Australia and an increasing number of people live with the condition. The main underlying cause is atherosclerosis, the formation of a plaque(s) within the vessel wall. To date, the best medical therapies reduce the relative risk of having a cardiovascular event by only 30-40%. There remains a considerable residual risk of patients experiencing a clinical event. A challenge now is to develop strategies to prevent these remaining cardiovascular events. As atherosclerosis is an inflammatory disease, then targeting pathways in the immune response is a potential option.
Aim: To delineate the altered monocyte state associated in individuals with increased biomedical cardiovascular risk factors, in particular determining the gene expression, epigenetic and functional changes that occur.
Westmead - Westmead Clinical School
We propose that monocytes - the main immune cell involved in atherosclerosis - are reprogrammed by biomedical risk factors to promote disease progression, and that many detrimental functional changes in monocytes persist, even after treatment to lower the risk factors.
How monocyte function is altered in the circulation of individuals with increased cardiovascular risk is largely unexplored, but is important to determine given that functional changes of monocytes in the circulation may promote the development and progression of atherosclerosis. We have preliminary evidence that monocytes adopt a pro-atherogenic phenotype in individuals with a perturbed lipid profile, but the full gamut of monocyte modifications associated with different biomedical CVD risk factors has not been fully interrogated.
To address this gap in knowledge, here we will identify the specific genes and pathways which are altered in monocytes from individuals with perturbed biomedical CVD risk factors and determine whether the differential expression of these genes can be explained by epigenetic modifications.
Our team includes scientists and clinicians giving the group the opportunity to conduct clinical studies with in depth scientific analysis.
The opportunity ID for this research opportunity is 2243