Influence of dendritic cell and macrophage on cholesterol absorption and excretion: implication in atherogenesis

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Copyright: Deswaerte, Virginie
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Abstract
Atherosclerosis represents the chronic pathophysiological process implicated in the majority of cardiovascular (CV). The development of atherosclerotic lesions is characterized by an accumulation of extracellular and intracellular lipids in the arterial wall and a strong local immuno-inflammatory response. We demonstrated that the longevity/ depletion of DCs and macrophages directly impacts atherosclerotic plaque formation and plasma cholesterol levels, which is a major main risk factor for atherosclerosis. To understand the inverse relationship between DC / macrophage numbers and cholesterolemia, we are evaluating the impact of these cells on cholesterol metabolism. In our CD11c-hBcl-2 mouse model, which is characterized by an enhanced DC lifespan, we observed an expanded tissue DC population associated with increased fecal sterol excretion and decreased cholesterol absorption and fecal bile acid excretion, compared to the control. Those observations were associated with a modification of the expression of genes involved in cholesterol metabolism in the liver and in the small intestine. We also found that DCs have an organ-specific impact on T cell development. In our Bcl-x mouse model, where macrophages were rendered more susceptible to apoptosis, we observed a reduced number of tissue macrophages. The lesions of these transgenic animals were more complex and unstable than those of controls. We also noted that there were associated increased levels of inflammatory cytokines. Taken together, the present studies reveal that DCs and macrophages are central to the atherosclerotic process, because they are directly implicated in both cholesterol turnover and immune response.
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Author(s)
Deswaerte, Virginie
Supervisor(s)
Jessup, Wendy
Lesnik, Philippe
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Publication Year
2012
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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