title: Cholesterol efflux pathways regulate myelopoiesis: a potential link to altered macrophage function in atherosclerosis.
abstract: Atherosclerotic cardiovascular disease is a chronic inflammatory disease of the blood vessels that can lead to myocardial infarction or stroke. The major cell in the atherosclerotic lesion, the macrophage, is thought to be an important contributor to the production of inflammatory mediators that exacerbate this disease. Macrophages are generally derived from circulating monocytes, which are in turn produced by hematopoietic stem and multipotential progenitor cells (HSPCs) in the bone marrow and other medullary organs. Recent studies suggest that disruption in cholesterol homeostasis or prolonged exposure to a hypercholesterolemic environment can influence HSPCs to over-produce monocytes, resulting in monocytosis. These monocytes may carry a pre-programed ability to become M1-like macrophages once they enter the atherosclerotic lesion. Future studies may help to differentiate the role of such pre-programing versus responses to local environmental cues in determining M1, M2, or other macrophage phenotypes in atherosclerotic lesions.
authors.affiliation: Haematopoiesis and Leukocyte Biology, Baker IDI , Melbourne, VIC , Australia ; Department of Immunology, Monash University , Melbourne, VIC , Australia ; University of New South Wales , Sydney, NSW , Australia.
authors.forename: Andrew James
authors.initials: AJ
authors.lastname: Murphy
authors.affiliation: Haematopoiesis and Leukocyte Biology, Baker IDI , Melbourne, VIC , Australia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Dragoljevic
authors.affiliation: Division of Molecular Medicine, Department of Medicine, Columbia University Medical Center , New York, NY , USA.
authors.forename: Alan Richard
authors.initials: AR
authors.lastname: Tall
keywords: HDL; atherosclerosis; cholesterol efflux; hematopoiesis; macrophages; monocytes