Hypercholesterolemia promotes early renal dysfunction in apolipoprotein E-deficient mice

Aging and dyslipidemia are processes which can lead to deleterious consequences to renal function. Therefore, the aim of this study was to determine the effects of both hypercholesterolemia and aging on renal function in mice. Male hypercholesterolemic apolipoprotein E-deficient mice (ApoE, n = 13)...

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Published in:	Lipids in health and disease Vol. 10; no. 1; p. 220
Main Authors:	Balarini, Camille M, Oliveira, Mariana Zt, Pereira, Thiago Mc, Silva, Nyam F, Vasquez, Elisardo C, Meyrelles, Silvana S, Gava, Agata L
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 26-11-2011 BioMed Central BMC
Subjects:	Age Factors Aging Animals Apolipoproteins Apolipoproteins E - deficiency Atherosclerosis Cholesterol Collagen Colleges & universities Complications and side effects Diet Fibrosis Gene Expression Genetic aspects Glomerular Filtration Rate Health sciences Hypercholesterolemia Hypercholesterolemia - complications Hypercholesterolemia - physiopathology Kidney - enzymology Kidney - pathology Kidney - physiopathology Kidney failure Kidney Tubules - pathology Kidneys Male Mice Mice, Inbred C57BL Mortality Nitric Oxide Synthase Type I - genetics Nitric Oxide Synthase Type I - metabolism Physiological aspects Proteins Renal Function Risk factors Rodents Science Statistical analysis Supervision Urea - blood Brazil
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Summary:	Aging and dyslipidemia are processes which can lead to deleterious consequences to renal function. Therefore, the aim of this study was to determine the effects of both hypercholesterolemia and aging on renal function in mice. Male hypercholesterolemic apolipoprotein E-deficient mice (ApoE, n = 13) and age-matched C57BL/6 control mice (C57, n = 15) were studied at 2 (young) and 8 (adult) month-old. At each time point, animals were placed in metabolic cages for 24 hours to urine volume and urinary creatinine quantification. Blood samples were collected for serum cholesterol, urea and creatinine measurements. Glomerular filtration rate (GFR) was estimated through creatinine clearance determination. Mesangial expansion was evaluated by Periodic Acid Schiff staining, renal fibrosis was determined through Masson's trichrome staining and neuronal nitric oxide synthase (nNOS) expression in the kidney was performed by Western Blotting. To statistical analysis two-way ANOVA followed by Fisher's post hoc test was used. Total plasma cholesterol was increased about 5-fold in ApoE mice at both time points compared to C57 animals. At 2-month-old, GFR was already markedly reduced in ApoE compared to C57 mice (187 ± 28 vs 358 ± 92 μL/min, p < 0.05). Adult C57 (-77%) and ApoE (-50%) mice also presented a significant reduction of GFR. In addition, serum urea was significantly increased in young ApoE animals compared to C57 mice (11 ± 1.3 vs 7 ± 0.9 mmol/L, p < 0.01). A significant mesangial expansion was observed at 2-month old ApoE mice compared to C57 mice (35 ± 0.6 vs 30 ± 0.9%, respectively, p < 0.05), which was aggravated at 8-month old animals (40 ± 3 and 35 ± 3%, respectively). Tubulointersticial fibrosis was augmented at both young (17 ± 2%, p < 0.05) and adult (20 ± 1%, p < 0.05) ApoE mice compared to respective C57 age controls (8 ± 1 and 12 ± 2%, respectively). The expression of nNOS was markedly reduced in a time-dependent manner in both strains. These data show that both hypercholesterolemia and aging contribute to the loss of renal function in mice.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1476-511X 1476-511X
DOI:	10.1186/1476-511x-10-220