Macrophage-derived apoESendaisuppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice

Hagai Tavori, Daping Fan, Ilaria Giunzioni, Lin Zhu, MacRae F. Linton, Agnes B. Fogo, Sergio Fazio

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    Abstract

    Lipoprotein glomerulopathy (LPG) is a renal disease often accompanied by dyslipidemia and increased serum apoE levels. apoESendai(Arg145Pro), a rare mutant based on the apoE3 sequence carrying an apoE2 charge, causes LPG in humans and transgenic mice, but its effects on the artery wall are unknown. Macrophage expression of apoESendaimay also directly influence renal and arterial homeostasis. We investigated the effects of macrophage-expressed apoESendaiin apoE-/-mice with or without LDL receptor (LDLR). Murine bone marrow transduced to express apoE2, apoE3, or apoESendaiwas transplanted into lethally irradiated mice. Macrophage apoESendaiexpression reduced aortic lesion size and inflammation by 32 and 28%, respectively, compared with apoE2 in apoE-/-recipients. No differences in lesion size or inflammation were found between apoESendaiand apoE3 in apoE-/-recipients. Macrophage apoESendaiexpression also reduced aortic lesion size by 18% and inflammation by 29% compared with apoE2 in apoE-/-/LDLR-/-recipients. Glomerular lesions compatible with LPG with increased mesangial matrix, extracellular lipid accumulation, and focal mesangiolysis were only observed in apoE-/-/LDLR-/-mice expressing apoESendai. Thus, macrophage expression of apoESendaiprotects against atherosclerosis while causing lipoprotein glomerulopathy. This is the first demonstration of an apoprotein variant having opposing effects on vascular and renal homeostasis.

    Original languageEnglish (US)
    Pages (from-to)2073-2081
    Number of pages9
    JournalJournal of Lipid Research
    Volume55
    Issue number10
    DOIs
    StatePublished - Oct 1 2014

    Fingerprint

    Apolipoprotein E2
    Macrophages
    Apolipoproteins E
    Lipoproteins
    Apolipoprotein E3
    Atherosclerosis
    LDL Receptors
    Low Density Lipoprotein Receptor-Related Protein-1
    Inflammation
    Kidney
    Homeostasis
    Glomerular Mesangium
    Apoproteins
    Dyslipidemias
    Transgenic Mice
    Blood Vessels
    Arteries
    Bone Marrow
    Lipoprotein Glomerulopathy
    Bone

    Keywords

    • Apolipoprotein E
    • Lipoprotein glomerulopathy
    • Macrophage

    ASJC Scopus subject areas

    • Biochemistry
    • Cell Biology
    • Endocrinology

    Cite this

    Macrophage-derived apoESendaisuppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice. / Tavori, Hagai; Fan, Daping; Giunzioni, Ilaria; Zhu, Lin; Linton, MacRae F.; Fogo, Agnes B.; Fazio, Sergio.

    In: Journal of Lipid Research, Vol. 55, No. 10, 01.10.2014, p. 2073-2081.

    Research output: Contribution to journalArticle

    Tavori, Hagai ; Fan, Daping ; Giunzioni, Ilaria ; Zhu, Lin ; Linton, MacRae F. ; Fogo, Agnes B. ; Fazio, Sergio. / Macrophage-derived apoESendaisuppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice. In: Journal of Lipid Research. 2014 ; Vol. 55, No. 10. pp. 2073-2081.
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    AU - Fan, Daping

    AU - Giunzioni, Ilaria

    AU - Zhu, Lin

    AU - Linton, MacRae F.

    AU - Fogo, Agnes B.

    AU - Fazio, Sergio

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    N2 - Lipoprotein glomerulopathy (LPG) is a renal disease often accompanied by dyslipidemia and increased serum apoE levels. apoESendai(Arg145Pro), a rare mutant based on the apoE3 sequence carrying an apoE2 charge, causes LPG in humans and transgenic mice, but its effects on the artery wall are unknown. Macrophage expression of apoESendaimay also directly influence renal and arterial homeostasis. We investigated the effects of macrophage-expressed apoESendaiin apoE-/-mice with or without LDL receptor (LDLR). Murine bone marrow transduced to express apoE2, apoE3, or apoESendaiwas transplanted into lethally irradiated mice. Macrophage apoESendaiexpression reduced aortic lesion size and inflammation by 32 and 28%, respectively, compared with apoE2 in apoE-/-recipients. No differences in lesion size or inflammation were found between apoESendaiand apoE3 in apoE-/-recipients. Macrophage apoESendaiexpression also reduced aortic lesion size by 18% and inflammation by 29% compared with apoE2 in apoE-/-/LDLR-/-recipients. Glomerular lesions compatible with LPG with increased mesangial matrix, extracellular lipid accumulation, and focal mesangiolysis were only observed in apoE-/-/LDLR-/-mice expressing apoESendai. Thus, macrophage expression of apoESendaiprotects against atherosclerosis while causing lipoprotein glomerulopathy. This is the first demonstration of an apoprotein variant having opposing effects on vascular and renal homeostasis.

    AB - Lipoprotein glomerulopathy (LPG) is a renal disease often accompanied by dyslipidemia and increased serum apoE levels. apoESendai(Arg145Pro), a rare mutant based on the apoE3 sequence carrying an apoE2 charge, causes LPG in humans and transgenic mice, but its effects on the artery wall are unknown. Macrophage expression of apoESendaimay also directly influence renal and arterial homeostasis. We investigated the effects of macrophage-expressed apoESendaiin apoE-/-mice with or without LDL receptor (LDLR). Murine bone marrow transduced to express apoE2, apoE3, or apoESendaiwas transplanted into lethally irradiated mice. Macrophage apoESendaiexpression reduced aortic lesion size and inflammation by 32 and 28%, respectively, compared with apoE2 in apoE-/-recipients. No differences in lesion size or inflammation were found between apoESendaiand apoE3 in apoE-/-recipients. Macrophage apoESendaiexpression also reduced aortic lesion size by 18% and inflammation by 29% compared with apoE2 in apoE-/-/LDLR-/-recipients. Glomerular lesions compatible with LPG with increased mesangial matrix, extracellular lipid accumulation, and focal mesangiolysis were only observed in apoE-/-/LDLR-/-mice expressing apoESendai. Thus, macrophage expression of apoESendaiprotects against atherosclerosis while causing lipoprotein glomerulopathy. This is the first demonstration of an apoprotein variant having opposing effects on vascular and renal homeostasis.

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