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

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Science  20 May 2010:
DOI: 10.1126/science.1189731


Elevated leukocyte cell numbers (leukocytosis), and monocytes in particular, promote atherosclerosis; however, how they become increased is poorly understood. Mice deficient in the ATP-binding cassette transporters ABCA1 and ABCG1, which promote cholesterol efflux from macrophages and suppress atherosclerosis in hypercholesterolemic mice, displayed leukocytosis, a transplantable myeloproliferative disorder, and a dramatic expansion of the stem and progenitor cell containing LinSca-1+Kit+ (LSK) population in the bone marrow. Transplantation of Abca1–/– Abcg1–/– bone marrow into apoA-1 transgenic mice with high HDL suppressed the LSK population, reduced leukocytosis, and reversed both the myeloproliferative disorder and accelerated atherosclerosis. The findings indicate that ABCA1, ABCG1, and HDL inhibit the proliferation of hematopoietic stem and multipotential progenitor cells and connect expansion of these populations with leukocytosis and accelerated atherosclerosis.