Effects of apolipoprotein M in uremic atherosclerosis.
Atherosclerosis
; 265: 93-101, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28866363
ABSTRACT
BACKGROUND AND AIMS:
Chronic kidney disease is characterized by uremia and causes premature death, partly due to accelerated atherosclerosis. Apolipoprotein (apo) M is a plasma carrier protein for the lipid sphingosine-1-phosphate (S1P). The Apom-S1P complex associates with HDL, and may contribute to its anti-atherosclerotic effects. The role of Apom/S1P in atherosclerosis is presently controversial and has not been explored in a uremic setting. We aimed to explore whether plasma concentrations of Apom/S1P are altered by uremia and whether Apom overexpression or deficiency affects classical and uremic atherosclerosis.METHODS:
Mild to moderate uremia was induced by subtotal nephrectomy (NX) in 86-92 Apoe-deficient mice that were either Apom-wild type, Apom-deficient, or overexpressed Apom (â¼10 fold). The effects of uremia on plasma Apom/S1P and atherosclerosis were evaluated and compared to non-nephrectomized controls.RESULTS:
Uremia increased plasma Apom by â¼25%, but not S1P. Plasma S1P was elevated by â¼300% in mice overexpressing Apom, and decreased by â¼25% in Apom-deficient mice. Apom overexpression augmented aortic root atherosclerosis and plasma cholesterol. In contrast, aortic arch atherosclerosis was unaffected by the Apom genotype. There was no effect of Apom-deficiency or Apom overexpression on uremic atherosclerosis.CONCLUSIONS:
This study highlights the complexity of Apom/S1P in atherosclerosis and challenges the notion that the Apom/S1P complex is anti-atherogenic, at least in Apoe-deficient mice.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doenças da Aorta
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Esfingosina
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Uremia
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Lisofosfolipídeos
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Aterosclerose
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Apolipoproteínas M
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Dinamarca