scholarly journals Overexpression and deletion of phospholipid transfer protein reduce HDL mass and cholesterol efflux capacity but not macrophage reverse cholesterol transport

2017 ◽  
Vol 58 (4) ◽  
pp. 731-741 ◽  
Author(s):  
Takashi Kuwano ◽  
Xin Bi ◽  
Eleonora Cipollari ◽  
Tomoyuki Yasuda ◽  
William R. Lagor ◽  
...  
2001 ◽  
Vol 360 (2) ◽  
pp. 379-385 ◽  
Author(s):  
Jessica LIE ◽  
Rini de CROM ◽  
Matti JAUHIAINEN ◽  
Teus van GENT ◽  
Rien van HAPEREN ◽  
...  

High-density lipoproteins (HDLs) are considered anti-atherogenic because they mediate peripheral cell cholesterol transport to the liver for excretion and degradation. An important step in this reverse cholesterol-transport pathway is the uptake of cellular cholesterol by a specific subclass of small, lipid-poor apolipoprotein A-I particles designated preβ-HDL. The two lipid-transfer proteins present in human plasma, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), have both been implicated in the formation of preβ-HDL. In order to investigate the relative contribution of each of these proteins, we used transgenic mouse models. Comparisons were made between human CETP transgenic mice (huCETPtg), human PLTP transgenic mice (huPLTPtg) and mice transgenic for both lipid-transfer proteins (huCETPtg/huPLTPtg). These animals showed elevated plasma levels of CETP activity, PLTP activity or both activities, respectively. We evaluated the generation of preβ-HDL in mouse plasma by immunoblotting and crossed immuno-electrophoresis. Generation of preβ-HDL was equal in huCETPtg and wild-type mice. In contrast, in huPLTPtg and huCETPtg/huPLTPtg mice, preβ-HDL generation was 3-fold higher than in plasma from either wild-type or huCETPtg mice. Our findings demonstrate that, of the two plasma lipid-transfer proteins, PLTP rather than CETP is responsible for the generation of preβ-HDL. These data support the hypothesis of a role for PLTP in the initial stage of reverse cholesterol transport.


2016 ◽  
Vol 241 (13) ◽  
pp. 1466-1472 ◽  
Author(s):  
Yanhong Si ◽  
Ying Zhang ◽  
Xiaofeng Chen ◽  
Lei Zhai ◽  
Guanghai Zhou ◽  
...  

Phospholipid transfer protein is expressed in various cell types and secreted into plasma, where it transfers phospholipids between lipoproteins and modulates the composition of high-density lipoprotein particles. Phospholipid transfer protein deficiency in vivo can lower high-density lipoprotein cholesterol level significantly and impact the biological quality of high-density lipoprotein. Considering high-density lipoprotein was a critical determinant for reverse cholesterol transport, we investigated the role of systemic phospholipid transfer protein deficiency in macrophage reverse cholesterol transport in vivo. After the littermate phospholipid transfer protein KO and WT mice were fed high-fat diet for one month, they were injected intraperitoneally with 3H-cholesterol-labeled and acLDL-loaded macrophages. Then the appearance of 3H-tracer in plasma, liver, bile, intestinal wall, and feces over 48 h was determined. Plasma lipid analysis indicated phospholipid transfer protein deficiency lowered total cholesterol, high-density lipoprotein-C and apolipoprotein A1 levels significantly but increased triglyceride level in mice. The isotope tracing experiment showed 3H-cholesterol of plasma was decreased by 68% for male and 62% for female, and 3H-tracer of bile was decreased by 37% for male and 21% for female in phospholipid transfer protein KO mice compared with WT mice. However, there was no difference in liver, and 3H-tracer of intestinal wall was increased by 43% for male and 27% for female. Finally, 3H-tracer of fecal excretion in phospholipid transfer protein KO mice was reduced significantly by 36% for male and 43% for female during 0–24 h period, but there was no significant difference during 24–48 h period. Meanwhile, Western Blot analysis showed the expressions of reverse cholesterol transport -related protein liver X receptor α (LXRα), ATP binding cassette transporter A1, and cholesterol 7α-hydroxylase A1 were upregulated in liver of phospholipid transfer protein KO mice compared with WT mice. These data reveal that systemic phospholipid transfer protein deficiency in mice impairs macrophage-specific reverse cholesterol transport in vivo.


2008 ◽  
Vol 283 (17) ◽  
pp. 11541-11549 ◽  
Author(s):  
John F. Oram ◽  
Gertrud Wolfbauer ◽  
Chongren Tang ◽  
W. Sean Davidson ◽  
John J. Albers

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