Atherosclerosis: Redefining the role of macrophages in atherosclerosis
Summary
We will redefine the role of macrophages in atherosclerosis -investigating the differing roles of macrophage subtypes in atherosclerosis and their relationship to plaque stability
Supervisor(s)
Research Location
Vascular Biology Research Centre, Westmead Hospital
Program Type
Masters/PHD
Synopsis
Atherosclerosis continues to be a major cause of morbidity and mortality in Australia. With ruptures more likely to occur in unstable atherosclerotic plaques (ones that have a relatively thin fibrous cap and large fatty core), the therapeutic goal is thus to convert unstable plaques to stable plaques. We propose that atherosclerotic plaque stability can be promoted by modulating monocyte/macrophage transformation. While monocytes have traditionally been known to play a detrimental role in cardiovascular disease by their transformation into macrophage foam cells, we have recently shown (in clinical samples) that monocytes contribute to the formation of the atherosclerotic cap by transforming into a macrophage subtype called a fibrocyte – a cell that exhibits both macrophage (expresses CD68, CD163 and presents antigen) and smooth muscle cell (SMC) characteristics, such as expression of SMC α-actin and production of collagen – factors which promote plaque stability. With macrophages known to adopt various functional phenotypes (inflammatory, immune regulation and wound healing subgroups) that can be sequentially converted from one phenotype to another, it may be possible to stabilise atherosclerotic plaques through modulating monocyte/ macrophage transformation. This project thus aims to understand the differing roles of macrophage subtypes in atherosclerosis and their relationship to plaque stability.
Additional Information
Techniques: This work will include a range of techniques such as immunohistochemistry, immunofluorescence and deconvolution microscopy, flow cytometry and cell culture. The team: Our team is composed of a mix of surgeons and scientists, with students at all levels from summer work experience through to post doc. Our research focus is on vascular wound models such as atherosclerosis and intimal hyperplasia with projects varying from clinical, laboratory (eg cell culture) through to small animal – all aimed at redefining the role of monocytes/macrophages in these conditions and thus identifying new pathways for therapeutic manipulation.
Want to find out more?
Contact Research Expert to find out more about participating in this opportunity.
Browse for other opportunities within the Vascular Biology Research Centre, Westmead Hospital .
Keywords
Heart disease, vascular disease, Wound healing, Progenitor cells, Monocytes, injury, Cardiovascular & respiratory diseases, Cell biology, Heart & circulation, Infection & immunity, atherosclerosis, macrophages, heart attack, blood vessel
Opportunity ID
The opportunity ID for this research opportunity is: 180
Other opportunities with Dr Heather Medbury