title: Phospholipid transfer protein deficiency in mice impairs macrophage reverse cholesterol transport in vivo.
abstract: 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 (3)H-cholesterol-labeled and acLDL-loaded macrophages. Then the appearance of (3)H-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 (3)H-cholesterol of plasma was decreased by 68% for male and 62% for female, and (3)H-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 (3)H-tracer of intestinal wall was increased by 43% for male and 27% for female. Finally, (3)H-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.
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian 271000, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Si
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian 271000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian 271000, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian 271000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhai
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian 271000, China.
authors.forename: Guanghai
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Taian Center Hospital, Taian 271000, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Yu
authors.affiliation: Taian Center Hospital, Taian 271000, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Cao
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian 271000, China shucunqin@hotmail.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shucun
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D049294:Phospholipid Transfer Proteins / Q000172:deficiency* / Q000235:genetics
chemical_list: D064286:ATP Binding Cassette Transporter 1; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; D000071518:Liver X Receptors; D049294:Phospholipid Transfer Proteins; C577833:Abca1 protein, mouse; C502772:Cyp7a1 protein, mouse
keywords: Phospholipid transfer protein; high-density lipoprotein; reverse cholesterol transport