Abstract
We reported that phospholipid transfer protein (PLTP) deficiency decreased atherosclerosis in mouse models. Because the decreased atherosclerosis was accompanied by a significant decrease in plasma HDL levels, we examined the properties of PLTP knockout (PLTP0) HDL and tested its ability to prevent LDL-induced monocyte chemotactic activity in human artery wall cell cocultures. We isolated HDL and LDL from LDL receptor knockout/PLTP knockout (LDLr0/PLTP0) mice and from apolipoprotein B transgenic (apoBTg)/PLTP0 mice as well as their controls. PLTP0 HDL was relatively rich in protein and depleted in phosphatidylcholine. Turnover studies revealed a 3.5- to 4.0-fold increase in the turnover of protein and cholesteryl ester in HDL from PLTP0 mice compared with control mice. The ability of HDL from LDLr0/PLTP0 and apoBTg/PLTP0 mice to prevent the induction of monocyte chemotactic activity in human artery wall cell cocultures exposed to human LDL was dramatically better than that in controls. Moreover, LDL from PLTP0 mice was markedly resistant to oxidation and induced significantly less monocyte chemotactic activity compared with that in controls. In vitro, PLTP0 HDL removed significantly more oxidized phospholipids from LDL than did control HDL. We conclude that PLTP deficiency improves the anti-inflammatory properties of HDL in mice and reduces the ability of LDL to induce monocyte chemotactic activity.
Highlights
We reported that phospholipid transfer protein (PLTP) deficiency decreased atherosclerosis in mouse models
apolipoprotein B-containing lipoprotein (BLp) secretion was diminished in hepatocytes from apolipoprotein B transgenic (apoBTg)/PLTP knockout (PLTP0) mice, a defect that was corrected when PLTP was reintroduced by adenoviral vector [7]
We demonstrated that a 2-fold increase in PLTP activity in mice mediated by adenovirus-associated virus infection resulted in 1) decreased HDL cholesterol, HDL phospholipid, and apoA-I levels; 2) decreased vitamin E content in total plasma and in individual lipoprotein fractions; 3) increased lipoprotein oxidation as assessed by copper-induced formation of conjugated dienes; 4) increased autoantibodies against oxidized apolipoprotein B (apoB)-containing particles; and 5) increased atherosclerotic lesions in the proximal aorta [12]
Summary
We reported that phospholipid transfer protein (PLTP) deficiency decreased atherosclerosis in mouse models. We conclude that PLTP deficiency improves the anti-inflammatory properties of HDL in mice and reduces the ability of LDL to induce monocyte chemotactic activity.—Yan, D., M. PLTP deficiency improves the anti-inflammatory properties of HDL and reduces the ability of LDL to induce monocyte chemotactic activity. In apoB transgenic (apoBTg) and apoE-0 backgrounds, PLTP deficiency resulted in reduced production and levels of BLp and markedly decreased atherosclerosis. PLTP deficiency increased vitamin E content in BLp in four mouse models of atherosclerosis, producing a dramatic delay in the generation of conjugated dienes in BLp as well as markedly lower titers of plasma IgG autoantibodies to oxidized LDL [8]. It was reported that a 2.5- to 4.5-fold increase in PLTP activity in PLTPTg mice resulted in a 30% to 40%
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