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.