Many studies have described an association between monocytosis and cardiovascular disease. This paper reports a mechanistic link between hypercholesterolaemia and monocytosis that helps to explain their combined effects on atherosclerosis. In the apolipoprotein E-deficient (Apoe−/−) mouse model of atherosclerosis, feeding a high-cholesterol diet results in increased proliferation of haematopoietic stem and multipotential progenitor cells (HSPCs), monocytosis and the increased entry of monocytes into atherosclerotic lesions, thereby enlarging the lesions. In wild-type mice, the authors observed high levels of APOE bound to proteoglycans on the surface of HSPCs, and this suppressed the proliferation of HSPCs in a cell-autonomous manner — probably by promoting cholesterol efflux from HSPCs. The results indicate that, in mice on a high-fat diet, a lack of cholesterol efflux from Apoe−/− HSPCs leads to membrane cholesterol accumulation and cell proliferation; this could be suppressed by the addition of the potent cholesterol acceptor high-density lipoprotein.
ORIGINAL RESEARCH PAPER
Murphy, A. J. et al. ApoE regulates hematopoietic stem cell proliferation, monocytosis, and monocyte accumulation in atherosclerotic lesions in mice. J. Clin. Invest. 121, 4138–4149 (2011)
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How a high-fat diet results in monocytosis. Nat Rev Immunol 11, 716 (2011). https://doi.org/10.1038/nri3104
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DOI: https://doi.org/10.1038/nri3104