Cholesterol efflux: a novel regulator of myelopoiesis and atherogenesisTall, A. R., Yvan-Charvet, L., Westerterp, M. & Murphy, A. J., Nov-2012, In : Arteriosclerosis, thrombosis, and vascular biology. 32, 11, p. 2547-2552 6 p.
Research output: Contribution to journal › Review article › Academic › peer-review
Monocytosis and neutrophilia are well-established risk factors for atherosclerosis and seem to play a causative role in lesion development. Studies in mice with defects in cholesterol efflux pathways have identified novel roles for the ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, and apolipoprotein E in suppressing hematopoietic stem cell proliferation, mobilization, and the production of monocytes and neutrophils in the bone marrow. In addition, stem cell mobilization to the spleen initiates extramedullary hematopoiesis, which acts as a monocytic reservoir. Increased monocyte and neutrophil levels drive atherogenesis and its complications. Increasing high-density lipoprotein levels and cholesterol efflux can reverse excessive myelopoiesis and stem cell mobilization, suggesting a novel antiatherogenic effect of some forms of high-density lipoprotein elevation. After a myocardial infarction, splenic Ly-6C(hi) monocyte populations are sustained by a second wave of stem cell mobilization from the bone marrow and continue to enter atheroma, accelerating atherogenesis. Because activation of cholesterol efflux pathways can inhibit stem cell proliferation, mobilization, and monocyte production, this may provide a rationale for boosting high-density lipoprotein levels after a myocardial infarction to prevent reocclusion.
|Number of pages||6|
|Journal||Arteriosclerosis, thrombosis, and vascular biology|
|Publication status||Published - Nov-2012|
- ATP-Binding Cassette Transporters/metabolism, Animals, Apolipoproteins E/metabolism, Atherosclerosis/etiology, Biological Transport, Cell Movement, Cell Proliferation, Cholesterol/metabolism, Feedback, Physiological, Hematopoietic Stem Cells/metabolism, Humans, Lipoproteins, HDL/metabolism, Monocytes/metabolism, Myelopoiesis, Myocardial Infarction/complications, Neutrophils/metabolism, Risk Factors