Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation
Abstract
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.
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The atheroprotective role of macrophage apoE has been well documented, with macrophage-derived apoE protecting against atherosclerosis during both early and late plaque development; protection remains even when expressed in low amounts and in the absence of changes in serum lipid levels.
“The atheroprotective role of macrophage apoE has been well documented, with macrophage-derived apoE being shown to protect against atherosclerosis during both early ( 12,13 ) and late plaque development ( 11 ); protection remains even when it is expressed in low amounts ( 14 ) and in the absence of changes in serum lipid levels ( 15 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [11]
Bone marrow transplantation is a reliable and validated approach to study the effect of changes in macrophage gene expression on atherosclerosis in the mouse.
“Bone marrow transplantation is a reliable and validated approach to study the effect of changes in macrophage gene expression on atherosclerosis in the mouse ( 2,11 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [11]
apoE was the first apoprotein studied in murine BMT experiments, and has been shown to affect atherosclerosis both by reducing serum lipid levels and by exerting local beneficial effects in the forming atheroma.
“apoE was the fi rst apoprotein studied in murine BMT experiments, and has been shown to affect atherosclerosis both by reducing serum lipid levels ( 11 ) and by exerting local benefi cial effects in the forming atheroma ( 43 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [11]
Macrophage expression of apoE influences both serum lipids and atherogenesis.
“Macrophage expression of apoE infl uences both serum lipids and atherogenesis ( 11 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [11]
About 90% of serum apoE is made in the liver and the remainder is produced by macrophages.
“About 90% of serum apoE is made in the liver ( 10 ) and the remainder is produced by macrophages ( 11 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [11]
Atherogenesis is influenced by macrophage expression of apoE.
“Atherogenesis is infl uenced by macrophage expression of apoE ( 11 ), the effects of which manifest as: 1 ) secretion into the circulation and association with lipoproteins to mediate their hepatic uptake ( 3, 6 ); and 2 ) modulation of the macrophage infl ammatory response in the atheroma ( 16,17 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [11]
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Self-citation
- Authors
- Linton, M. F., Atkinson, J. B., & Fazio, S.
- Affiliations
- Vanderbilt University (US)
- Venue
- Science
- Published
- 1995-02-17
- Volume
- 267
- Issue
- 5200
- Pages
- 1034-1037
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2028841673
- Cited by
- 478
- References
- 5
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 4 · 2023: 10 · 2022: 8 · 2021: 5 · 2020: 6 · 2019: 14 · 2018: 9 · 2017: 7 · 2016: 9 · 2015: 22 · 2014: 16 · 2013: 9 · 2012: 20
- FWCI
- 25.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08hl002925-03)
- National Heart, Lung, and Blood Institute (HL-02925)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-26657-15, P30DK026657)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein E deficiency, atherosclerosis prevention, bone marrow transplantation, hyperlipidemia, lipoprotein clearance, serum cholesterol, diet-induced atherosclerosis, gene-targeted mice
- MeSH terms
- Animals, Aortic Diseases, Apolipoproteins E, Arteriosclerosis, Cholesterol, Coronary Artery Disease, Lipoproteins, Lipoproteins, LDL, Lipoproteins, VLDL, Macrophages, Mice, Inbred C57BL, Bone Marrow Transplantation, Mice, Lipoproteins, IDL
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