Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice[S]
LCAT, a plasma enzyme that esterifies cholesterol, has been proposed to play an antiatherogenic role, but animal and epidemiologic studies have yielded conflicting results. To gain insight into LCAT and the role of free cholesterol (FC) in atherosclerosis, we examined the effect of LCAT over- and un...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-07-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520355486 |
| _version_ | 1819127477780348928 |
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| author | Seth G. Thacker Xavier Rousset Safiya Esmail Abdalrahman Zarzour Xueting Jin Heidi L. Collins Maureen Sampson John Stonik Stephen Demosky Daniela A. Malide Lita Freeman Boris L. Vaisman Howard S. Kruth Steven J. Adelman Alan T. Remaley |
| author_facet | Seth G. Thacker Xavier Rousset Safiya Esmail Abdalrahman Zarzour Xueting Jin Heidi L. Collins Maureen Sampson John Stonik Stephen Demosky Daniela A. Malide Lita Freeman Boris L. Vaisman Howard S. Kruth Steven J. Adelman Alan T. Remaley |
| author_sort | Seth G. Thacker |
| collection | DOAJ |
| description | LCAT, a plasma enzyme that esterifies cholesterol, has been proposed to play an antiatherogenic role, but animal and epidemiologic studies have yielded conflicting results. To gain insight into LCAT and the role of free cholesterol (FC) in atherosclerosis, we examined the effect of LCAT over- and underexpression in diet-induced atherosclerosis in scavenger receptor class B member I-deficient [Scarab(−/−)] mice, which have a secondary defect in cholesterol esterification. Scarab(−/−)×LCAT-null [Lcat(−/−)] mice had a decrease in HDL-cholesterol and a high plasma ratio of FC/total cholesterol (TC) (0.88 ± 0.033) and a marked increase in VLDL-cholesterol (VLDL-C) on a high-fat diet. Scarab(−/−)×LCAT-transgenic (Tg) mice had lower levels of VLDL-C and a normal plasma FC/TC ratio (0.28 ± 0.005). Plasma from Scarab(−/−)×LCAT-Tg mice also showed an increase in cholesterol esterification during in vitro cholesterol efflux, but increased esterification did not appear to affect the overall rate of cholesterol efflux or hepatic uptake of cholesterol. Scarab(−/−)×LCAT-Tg mice also displayed a 51% decrease in aortic sinus atherosclerosis compared with Scarab(−/−) mice (P < 0.05). In summary, we demonstrate that increased cholesterol esterification by LCAT is atheroprotective, most likely through its ability to increase HDL levels and decrease pro-atherogenic apoB-containing lipoprotein particles. |
| first_indexed | 2024-12-22T08:12:33Z |
| format | Article |
| id | doaj.art-5c6c0d928d984e2f80593e0d1360a62d |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-22T08:12:33Z |
| publishDate | 2015-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-5c6c0d928d984e2f80593e0d1360a62d2022-12-21T18:32:59ZengElsevierJournal of Lipid Research0022-22752015-07-0156712821295Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice[S]Seth G. Thacker0Xavier Rousset1Safiya Esmail2Abdalrahman Zarzour3Xueting Jin4Heidi L. Collins5Maureen Sampson6John Stonik7Stephen Demosky8Daniela A. Malide9Lita Freeman10Boris L. Vaisman11Howard S. Kruth12Steven J. Adelman13Alan T. Remaley14Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892Experimental Atherosclerosis Section, Center for Molecular, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892Vascular Strategies LLC, Plymouth Meeting, PA 19462Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892Light Microscopy Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892Experimental Atherosclerosis Section, Center for Molecular, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892Vascular Strategies LLC, Plymouth Meeting, PA 19462To whom correspondence should be addressed; Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; To whom correspondence should be addressedLCAT, a plasma enzyme that esterifies cholesterol, has been proposed to play an antiatherogenic role, but animal and epidemiologic studies have yielded conflicting results. To gain insight into LCAT and the role of free cholesterol (FC) in atherosclerosis, we examined the effect of LCAT over- and underexpression in diet-induced atherosclerosis in scavenger receptor class B member I-deficient [Scarab(−/−)] mice, which have a secondary defect in cholesterol esterification. Scarab(−/−)×LCAT-null [Lcat(−/−)] mice had a decrease in HDL-cholesterol and a high plasma ratio of FC/total cholesterol (TC) (0.88 ± 0.033) and a marked increase in VLDL-cholesterol (VLDL-C) on a high-fat diet. Scarab(−/−)×LCAT-transgenic (Tg) mice had lower levels of VLDL-C and a normal plasma FC/TC ratio (0.28 ± 0.005). Plasma from Scarab(−/−)×LCAT-Tg mice also showed an increase in cholesterol esterification during in vitro cholesterol efflux, but increased esterification did not appear to affect the overall rate of cholesterol efflux or hepatic uptake of cholesterol. Scarab(−/−)×LCAT-Tg mice also displayed a 51% decrease in aortic sinus atherosclerosis compared with Scarab(−/−) mice (P < 0.05). In summary, we demonstrate that increased cholesterol esterification by LCAT is atheroprotective, most likely through its ability to increase HDL levels and decrease pro-atherogenic apoB-containing lipoprotein particles.http://www.sciencedirect.com/science/article/pii/S0022227520355486lecithin:cholesterol acyltransferasescavenger receptor class B member Iknockout |
| spellingShingle | Seth G. Thacker Xavier Rousset Safiya Esmail Abdalrahman Zarzour Xueting Jin Heidi L. Collins Maureen Sampson John Stonik Stephen Demosky Daniela A. Malide Lita Freeman Boris L. Vaisman Howard S. Kruth Steven J. Adelman Alan T. Remaley Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice[S] Journal of Lipid Research lecithin:cholesterol acyltransferase scavenger receptor class B member I knockout |
| title | Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice[S] |
| title_full | Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice[S] |
| title_fullStr | Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice[S] |
| title_full_unstemmed | Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice[S] |
| title_short | Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice[S] |
| title_sort | increased plasma cholesterol esterification by lcat reduces diet induced atherosclerosis in sr bi knockout mice s |
| topic | lecithin:cholesterol acyltransferase scavenger receptor class B member I knockout |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520355486 |
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