Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation.
Apolipoprotein E (apoE) deficiency causes severe hyperlipidemia and atherosclerosis in humans and in gene-targeted mice. Although the majority of apoE in plasma is of hepatic origin, apoE is synthesized by a variety of cell types, including macrophages. Because macrophages derive from hematopoietic cells, bone marrow transplantation was used to examine the potential of apoE synthesized by bone marrow-derived cells to correct the hyperlipidemia and atherosclerosis caused by apoE deficiency. After transplantation of bone marrow from mice with the normal apoE gene into apoE-deficient mice, apoE was detected in serum and promoted clearance of lipoproteins and normalization of serum cholesterol levels. ApoE-deficient mice given transplants of normal bone marrow showed virtually complete protection from diet-induced atherosclerosis.
Linton
M F
MF
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2250.
Atkinson
J B
JB
Fazio
S
S
D000818:Animals; D001018:Aortic Diseases / Q000517:prevention & control; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000517:prevention & control*; D016026:Bone Marrow Transplantation; D002784:Cholesterol / Q000097:blood*; D003324:Coronary Artery Disease / Q000517:prevention & control; D008074:Lipoproteins / Q000097:blood*; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
D001057:Apolipoproteins E; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D002784:Cholesterol