Macrophage phospholipid transfer protein deficiency and ApoE secretion: impact on mouse plasma cholesterol levels and atherosclerosis.
OBJECTIVE
PLTP and apoE play important roles in lipoprotein metabolism and atherosclerosis. It is known that formation of macrophage-derived foam cells (which highly express PLTP and apoE) is the critical step in the process of atherosclerosis. We investigated the relationship between PLTP and apoE in macrophages and the atherogenic relevance in a mouse model.


RESULTS
We transplanted PLTP-deficient mouse bone marrow into apoE-deficient mice (PLTP-/- --> apoE-/-), creating a mouse model with PLTP deficiency and apoE expression exclusively in the macrophages. We found that PLTP-/- --> apoE-/- mice have significantly lower PLTP activity, compared with controls (WT --> apoE-/-; 20%, P<0.01). On a Western diet, PLTP-/- --> apoE-/- mice have significantly lower plasma apoE than that of WT --> apoE-/- mice (63%, P<0.001), and PLTP-deficient macrophages secrete significantly less apoE than WT macrophages (44%, P<0.01). Moreover, PLTP-/- --> apoE-/- mice have significantly higher plasma cholesterol (98%, P<0.001) and phospholipid (107%, P<0.001) than that of WT --> apoE-/- mice, thus increasing atherosclerotic lesions in the aortic arch and root (403%, P<0.001), as well as the entire aorta (298%, P<0.001).


CONCLUSIONS
Macrophage PLTP deficiency causes a significant reduction of apoE secretion from the cells, and this in turn promotes the accumulation of cholesterol in the circulation and accelerates the development of atherosclerosis.
Liu
Ruijie
R
Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, 450 Clarkson Ave, Brooklyn, NY 11203, USA.
Hojjati
Mohammad R
MR
Devlin
Cecilia M
CM
Hansen
Inge H
IH
Jiang
Xian-Cheng
XC
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000097:blood* / Q000209:etiology* / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000473:pathology; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood*; D004195:Disease Models, Animal; D018450:Disease Progression; D004198:Disease Susceptibility; D005260:Female; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000097:blood; D012307:Risk Factors
D001057:Apolipoproteins E; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; D002784:Cholesterol