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Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI.

Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI. Research Abstract Details 

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  • Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI. Abstract Text:

    patricia g yanceyPatricia G Yancey,w gray jeromeW Gray Jerome,hong yuHong Yu,evelyn e griffinEvelyn E Griffin,brian e coxBrian E Cox,vladimir r babaevVladimir R Babaev,sergio fazioSergio Fazio,macrae f lintonMacRae F Linton,

    Mice deficient in scavenger receptor class B type I (SR-BI) and apolipoprotein E (apoE) [double knockout (DKO) mice] develop dyslipidemia, accelerated atherosclerosis, and myocardial infarction, and die prematurely. We examined effects of apoE and SR-BI deficiency on macrophage cholesterol homeostasis. DKO macrophages had increased total cholesterol (TC) stores (220-380 microg/mg protein) compared with apoE-/- cells (40 microg/mg), showed significant lysosomal lipid engorgement, and increased their TC by 34% after exposure to HDL. DKO macrophages from apoE-/- mice reconstituted with DKO bone marrow showed less cholesterol accumulation (89 microg/mg), suggesting that the dyslipidemia of DKO mice explains part of the cellular cholesterol defect. However, analyses of DKO and apoE-/- macrophages from transplanted apoE-/- mice revealed a role for macrophage SR-BI, inasmuch as the TC in DKO macrophages increased by 10% in the presence of HDL, whereas apoE-/- macrophage TC decreased by 33%. After incubation with HDL, the free cholesterol (FC) increased by 29% in DKO macrophages, and decreased by 8% in apoE-/- cells, and only DKO cells had FC in large peri-nuclear pools. Similar trends were observed with apoA-I as an acceptor. Thus, the abnormal cholesterol homeostasis of DKO macrophages is due to the plasma lipid environment of DKO mice and to altered trafficking of macrophage cholesterol. Both factors are likely to contribute to the accelerated atherosclerosis in DKO mice.

    Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI. Publishing Authors By Initials

    pg yanceyPG Yancey,wg jeromeWG Jerome,h yuH Yu,ee griffinEE Griffin,be coxBE Cox,vr babaevVR Babaev,s fazioS Fazio,mf lintonMF Linton,

    For similar diagnosis: diagnostic techniques and procedures: diagnostic imaging: microscopy: microscopy, electron research abstracts see: diagnosis: diagnostic techniques and procedures: diagnostic imaging: microscopy: microscopy, electron research

    PUBMED ID PMID:

    MEDLINE DATE:

    Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Journal of lipid research

    VOLUME: 48

    Page Numbers: 1140-9

    Journal Abbreviation:

    ISSN: 0022-2275

    DAY: 13

    MONTH: 02

    YEAR: 2007

    Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 376606

    Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI. Keywords Mesh Terms:

    KEYWORDS: Microscopy, Electron

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI. Information

    Substance Name: Cholesterol

    Registry Number: 57-88-5

    Grant and Affiliation Information for Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI.

    AFFILIATION: Atherosclerosis Research Unit, Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. patricia.g.yancey@vanderbilt.edu

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NHLBI

    GRANT: HL-65709

    ACRONYM: HL

    MEDLINETA: J Lipid Res

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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