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What role do local stem cells play in atherosclerosis?

Associate Professor Peter Psaltis, Institution: University of Adelaide

2019 Vanguard Grant

Years funded: 2020-2021


Atherosclerosis is the build-up of fatty plaques inside the body’s arteries. As the main cause of heart attack and stroke, it is the leading cause of death worldwide. We need to better understand how atherosclerosis occurs to improve the ways we treat it. Although most atherosclerosis research focuses on the development of plaque itself, an important but under-recognised aspect of the disease are changes that take place in the outer layer of the artery wall (or adventitia). These involve expansion of inflammatory cells, called macrophages and tiny blood vessels, called vasa vasorum, that together feed the growth of plaque from the outside of the artery in.

How these changes occur remains unclear. In a world-first, we have discovered a population of “stem cells” nestled in the adventitia of arteries that originate from specialised stem cells in early embryonic life. These stem cells, which we call haemangoblasts, produce both macrophages and the endothelial cells that line blood vessels. In this project, we will use sophisticated experimental techniques and unique mouse models, to study what happens to these haemangioblasts in different stages of atherosclerosis from early disease through to established and advanced atherosclerotic plaques.

We will investigate whether these haemangioblasts expand and contribute to macrophages and vasa vasorum in the adventitia and plaque of atherosclerotic arteries, and whether they aggravate and destabilise atherosclerotic lesions. We will also analyse the genes that haemangioblasts express to get a better understanding of how these unique stem cells are controlled in healthy arteries and how they change when atherosclerosis occurs. The lessons learnt from our research could change the way scientists think about atherosclerosis and pave the way for the development and testing of new treatments that target adventitial haemangioblasts to impact on the enormous burden that atherosclerosis causes human health.

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