Invited Speaker


The Monocyte/Macrophage as a Promising Therapeutic Target for Atherosclerosis
Dipak Purshottam Ramji, James E. McLaren, Na Li, Rebecca Salter, Nishi N. Singh, Daryn Michael, Timothy Ashlin
U.K

Atherosclerosis, the underlying cause of heart attacks and strokes, is a major cause of morbidity and mortality worldwide. Atherosclerosis is an inflammatory disorder orchestrated by cytokines, with monocytes/macrophages involved at all stages of the disease. Indeed, the recruitment of monocytes to the activated endothelium, their differentiation into macrophages and subsequent transformation into lipid-loaded foam cells, and the ensuing inflammatory response represent critical early events in the pathogenesis of atherosclerosis. The regulation of macrophage activities therefore represents a promising strategy for the prevention and treatment of atherosclerosis. It is thus essential that the molecular mechanisms underlying the changes in macrophage properties and function during this disease are thoroughly understood. We have therefore been investigating the signalling pathways and the underlying mechanisms through which cytokines regulate macrophage foam cell formation and the inflammatory response. Our studies have provided novel insights into the actions of several cytokines, including interferon-gamma, transforming growth factor-beta and the tumour necrosis factor family. In addition, we have identified the potential mechanisms through which cholesterol lowering drugs (statins) and activators of nuclear receptors limit inflammatory gene expression in macrophages. These findings will be presented in the context of available and future approaches that target monocytes/macrophages as therapeutic targets for atherosclerosis.

Funding: British Heart Foundation