title: Vitamin E protection of obesity-enhanced vascular calcification in uremic rats.
abstract: This study aimed to determine the extent of extraskeletal calcification in uremic Zucker rats, by comparing obese and lean phenotypes, and to evaluate the influence of vitamin E (VitE) on the development of calcifications in both uremic rats and human vascular smooth muscle cells (HVSMCs) cultured in vitro. Zucker rats of lean and obese phenotypes with normal renal function [control (C); C-lean and C-obese groups] and with uremia [5/6 nephrectomy (Nx); Nx-lean and Nx-obese groups] and uremic rats treated with VitE (Nx-lean + VitE and Nx-obese + VitE groups) were studied. Uremic groups were subjected to Nx, fed a 0.9% phosphorus diet, and treated with calcitriol (80 ng/kg ip). The aortic calcium concentration was significantly higher (P < 0.05) in Nx-obese rats (10.0 ± 2.1 mg/g tissue) than in Nx-lean rats (3.6 ± 1.3 mg/g tissue). A decrease in plasma glutathione peroxidase activity was observed in Nx-obese rats compared with Nx-lean rats (217.2 ± 18.2 vs. 382.3 ± 15.5 nmol·min(-1)·ml(-1), P < 0.05). Treatment with VitE restored glutathione peroxidase activity and reduced the aortic calcium concentration to 4.6 ± 1.3 mg/g tissue. The differences in mineral deposition between Nx-lean, Nx-obese, Nx-lean + VitE, and Nx-obese + VitE rats were also evidenced in other soft tissues. In HVSMCs incubated with high phosphate, VitE also prevented oxidative stress and reduced calcium content, bone alkaline phosphatase, and gene expression of core-binding factor-α1. In conclusion, uremic obese rats develop more severe calcifications than uremic lean rats and VitE reduces oxidative stress and vascular calcifications in both rats and cultures of HVSMCs.
authors.affiliation: Lipid and Arteriosclerosis Unit, IMBIC, Reina Sofia University Hospital, Avda Menendez Pidal s/n, 14004, Cordoba, Spain. yolandaalmaden@yahoo.es.
authors.forename: A
authors.initials: A
authors.lastname: Peralta-Ramírez
authors.forename: A
authors.initials: A
authors.lastname: Montes de Oca
authors.forename: A I
authors.initials: AI
authors.lastname: Raya
authors.forename: C
authors.initials: C
authors.lastname: Pineda
authors.forename: I
authors.initials: I
authors.lastname: López
authors.forename: F
authors.initials: F
authors.lastname: Guerrero
authors.forename: E
authors.initials: E
authors.lastname: Diez
authors.forename: J R
authors.initials: JR
authors.lastname: Muñoz-Castañeda
authors.forename: J
authors.initials: J
authors.lastname: Martinez
authors.forename: Y
authors.initials: Y
authors.lastname: Almaden
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez
authors.forename: E
authors.initials: E
authors.lastname: Aguilera-Tejero
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D011924:Rats, Zucker; D014511:Uremia / Q000150:complications / Q000473:pathology*; D061205:Vascular Calcification / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control*; D014810:Vitamin E / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014810:Vitamin E; D005979:Glutathione Peroxidase; D002118:Calcium
keywords: obesity; rat; vascular calcification; vitamin E