title: Hypercholesterolemia promotes early renal dysfunction in apolipoprotein E-deficient mice.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These data show that both hypercholesterolemia and aging contribute to the loss of renal function in mice.
authors: Laboratory of Transgenes and Cardiovascular Control, Physiological Sciences Graduate Program, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors: Camille M
authors: CM
authors: Balarini
authors: Mariana Zt
authors: MZ
authors: Oliveira
authors: Thiago Mc
authors: TM
authors: Pereira
authors: Nyam F
authors: NF
authors: Silva
authors: Elisardo C
authors: EC
authors: Vasquez
authors: Silvana S
authors: SS
authors: Meyrelles
authors: Agata L
authors: AL
authors: Gava
mesh_terms: D000367:Age Factors; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D005355:Fibrosis; D015870:Gene Expression; D005919:Glomerular Filtration Rate; D006937:Hypercholesterolemia / Q000150:complications* / Q000503:physiopathology; D007668:Kidney / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D014508:Urea / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D014508:Urea; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse