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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Lipid+Res
2014 ; 55
(10
): 2073-81
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Macrophage-derived apoESendai suppresses atherosclerosis while causing
lipoprotein glomerulopathy in hyperlipidemic mice
#MMPMID25183802
Tavori H
; Fan D
; Giunzioni I
; Zhu L
; Linton MF
; Fogo AB
; Fazio S
J Lipid Res
2014[Oct]; 55
(10
): 2073-81
PMID25183802
show ga
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 apoESendai may also directly influence renal and arterial
homeostasis. We investigated the effects of macrophage-expressed apoESendai in
apoE(-/-) mice with or without LDL receptor (LDLR). Murine bone marrow transduced
to express apoE2, apoE3, or apoESendai was transplanted into lethally irradiated
mice. Macrophage apoESendai expression 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
apoESendai and apoE3 in apoE(-/-) recipients. Macrophage apoESendai expression
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 apoESendai protects against
atherosclerosis while causing lipoprotein glomerulopathy. This is the first
demonstration of an apoprotein variant having opposing effects on vascular and
renal homeostasis.