The Macrophage Foam Cell as a Promising Therapeutic Target for Atherosclerosis
Dipak P. Ramji, James E. McLaren, Na Li, Rebecca Salter, Daryn Michael and Tim Ashlin Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff, Wales, UK
Abstract:
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 macrophages involved at all stages of the disease. The transformation of macrophages into lipid-loaded foam cells represents a critical early step in this disease. The regulation of macrophage foam cell formation therefore represents a promising strategy for the prevention and treatment of atherosclerosis. It is thus essential that the molecular mechanisms underlying this are fully understood. We have therefore been investigating the signalling pathways and the underlying mechanisms through which cytokines regulate macrophage foam cell formation along with the inflammatory response. Our studies have provided novel insights into the actions of several cytokines, including interferon-gamma, transforming growth factor-beta, tumour necrosis factor-like protein 1A, interleukin-17 and interleukin-33. In addition, we have identified the potential mechanisms through which cholesterol lowering drugs (statins) and activators of nuclear receptors affect the macrophage inflammatory response. These findings will be presented in the context of available and future approaches that target the macrophage foam cell as therapeutic targets for atherosclerosis.
