Abstract
BackgroundAging 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.MethodsMale 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.ResultsTotal 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.ConclusionsThese data show that both hypercholesterolemia and aging contribute to the loss of renal function in mice.
Highlights
Aging and dyslipidemia are processes which can lead to deleterious consequences to renal function
The murine model that lacks the functional gene encoding the apolipoprotein E (ApoE), which spontaneously develops hypercholesterolemia and atherosclerotic lesions similar to those found in human beings [7,8] has greatly contributed to the understanding of these disorders
In the present study we aim to evaluate the effects of both hypercholesterolemia and aging on renal function in the murine model of spontaneous atherosclerosis compared to the normocholesterolemic C57BL/6 (C57) mouse
Summary
Aging and dyslipidemia are processes which can lead to deleterious consequences to renal function. The aim of this study was to determine the effects of both hypercholesterolemia and aging on renal function in mice. Besides its relation with cardiovascular events, hypercholesterolemia is considered a factor that contributes to renal dysfunction [5] and to worsening the state of patients with previous kidney damage [6]. Patients with dyslipidemia usually show cardiovascular manifestations, few studies have focused on the deleterious effects of hypercholesterolemia on the progression of renal disease. Dyslipidemia and aging are known to be risk factors for renal diseases, there is a lack of studies concerning the effects of these conditions together in the ApoE mouse
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