title: Vitamin D receptor activation, left ventricular hypertrophy and myocardial fibrosis.
abstract: BACKGROUND
  Left ventricular hypertrophy (LVH), a common complication in chronic kidney disease (CKD), is associated with high cardiovascular mortality. The aim of this experimental study was to analyze the effect of different vitamin D receptor activators (VDRAs) on both LVH and myocardial fibrosis in chronic renal failure (CRF).
  
  
  METHODS
  Male Wistar rats with CRF, carried out by 7/8 nephrectomy, were treated intraperitoneally with equivalent doses of VDRAs (calcitriol, paricalcitol and alfacalcidol, 5 days per week) during 4 weeks. A placebo group (CRF + vehicle) and a Sham group with normal renal function served as controls. Biochemical, morphological, functional and molecular parameters associated with LVH were evaluated, as well as cardiac fibrosis, collagen I, transforming growth factor β1 (TGFβ1) and matrix metalloproteinase-1 (MMP1) expression.
  
  
  RESULTS
  All VDRAs treatment prevented LVH, with values of cardiomyocyte size, LV wall and septum thickness and heart-body weight ratio similar to those observed in the Sham group. At molecular levels, all VDRAs attenuated atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression compared with CRF + vehicle. The phosphorylation of ERK1/2, a signal for activating growth, was stimulated in the CRF + vehicle group; VDRAs use prevented this activation. Paricalcitol was the only VDRA used that maintained in the normal range all parameters associated with myocardial fibrosis (total collagen, collagen I, TGFβ1 and MMP1).
  
  
  CONCLUSIONS
  Our findings demonstrated that the three VDRAs used induced similar changes in bone metabolic parameters and LVH. In addition, paricalcitol was the only VDRA which showed a relevant beneficial effect in the reduction of myocardial fibrosis, a key factor in the myocardial dysfunction in CKD patients.
authors.affiliation: Servicio de Metabolismo Óseo y Mineral. Instituto Reina Sofía de Investigación. REDinREN del ISCIII. Universidad de Oviedo. Hospital Universitario Central de Asturias, Oviedo, España.
authors.forename: Sara
authors.initials: S
authors.lastname: Panizo
authors.forename: Sara
authors.initials: S
authors.lastname: Barrio-Vázquez
authors.forename: Manuel
authors.initials: M
authors.lastname: Naves-Díaz
authors.forename: Natalia
authors.initials: N
authors.lastname: Carrillo-López
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez
authors.forename: Amalia
authors.initials: A
authors.lastname: Fernández-Vázquez
authors.forename: Jose M
authors.initials: JM
authors.lastname: Valdivielso
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Cannata-Andía
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002117:Calcitriol / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004872:Ergocalciferols / Q000627:therapeutic use; D005355:Fibrosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications; D020935:MAP Kinase Signaling System; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D018167:Receptors, Calcitriol / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D006887:Hydroxycholecalciferols; D018167:Receptors, Calcitriol; D020097:Natriuretic Peptide, Brain; C084656:paricalcitol; D009320:Atrial Natriuretic Factor; D002117:Calcitriol; C008088:alfacalcidol
keywords: CKD; LVH; VDRAs; myocardial fibrosis