ATP-Binding Cassette Transporters and HDL Suppress Hematopoietic Stem Cell Proliferation

Abstract

Inhibiting Leukocytosis Leukocytosis—an elevated white blood cell count—contributes by unknown mechanisms to the pathogenesis of atherosclerosis and associated coronary heart disease. Now, Yvan-Charvet et al. (p. 1689 , published online 20 May; see the Perspective by Hansson and Björkholm ) show that the adenosine triphosphate–binding cassette transporters ABCA1 and ABCG1 are critical suppressors of atherosclerosis-associated leukocytosis. Mice deficient in both transporters in blood-producing hematopoietic cells possessed increased levels of hematopoietic stem and multipotential progenitor cells and accelerated atherosclerosis. ABCA1 and ABGA1 protect against atherosclerosis by promoting cholesterol efflux from cholesterol-laden macrophage foam cells to lipid-poor high-density lipoprotein (HDL) and apolipoprotein A-1. The leukocytosis and atherosclerosis in ABCA1- and ABG1-deficient mice were reversed in the presence of high amounts of HDL. Thus, signaling already known to inhibit atherosclerosis by reducing cholesterol in atherosclerotic plaques also reduces atherosclerosis-associated leukocytosis.