title: Parathyroid hormone and phosphorus overload in uremia: impact on cardiovascular system.
abstract: BACKGROUND
  Cardiac remodeling in uremia is characterized by left ventricular hypertrophy, interstitial fibrosis and microvascular disease. Cardiovascular disease is the leading cause of death in uremic patients, but coronary events alone are not the prevalent cause, sudden death and heart failure are. We studied the cardiac remodeling in experimental uremia, evaluating the isolated effect of parathyroid hormone (PTH) and phosphorus.
  
  
  METHODS
  Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx); they also received vehicle (V) and PTH at normal (nPTH) or high (hPTH) doses. They were fed with a poor-phosphorus (pP) or rich-phosphorus (rP) diet and were divided into the following groups: 'Sham': G1 (V+normal-phosphorus diet (np)) and 'Nx+PTx': G2 (nPTH+pP), G3 (nPTH+rP), G4 (hPTH+pP) and G5 (hPTH+rP). After 8 weeks, biochemical analysis, myocardium morphometry and arteriolar morphological analysis were performed. In addition, using immunohistochemical analysis, we evaluated angiotensin II, α-actin, transforming growth factor-beta (TGF-β) and nitrotyrosine, as well as fibroblast growth factor-23 (FGF-23), fibroblast growth factor receptor-1 (FGFR-1) and runt-related transcription factor-2 (Runx-2) expression.
  
  
  RESULTS
  Nx animals presented higher serum creatinine levels as well as arterial hypertension. Higher PTH levels were associated with myocardial hypertrophy and fibrosis as well as a higher coronary lesion score. High PTH animals also presented a higher myocardial expression of TGF-β, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of α-actin. Phosphorus overload was associated with higher serum FGF-23 levels and Runx-2, as well as myocardial hypertrophy. FGFR-1 was positive in the cardiomyocytes of all groups as well as in calcified coronaries of G4 and G5 whereas Runx-2 was positive in G3, G4 and G5.
  
  
  CONCLUSIONS
  In uremia, PTH and phosphorus overload are both independently associated with major changes related to the cardiac remodeling process, emphasizing the need for a better control of these factors in chronic kidney disease.
authors.affiliation: Department of Internal Medicine, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Melani R
authors.initials: MR
authors.lastname: Custódio
authors.forename: Marcia K
authors.initials: MK
authors.lastname: Koike
authors.forename: Katia R
authors.initials: KR
authors.lastname: Neves
authors.forename: Luciene M
authors.initials: LM
authors.lastname: dos Reis
authors.forename: Fabiana G
authors.initials: FG
authors.lastname: Graciolli
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Neves
authors.forename: Daniella G
authors.initials: DG
authors.lastname: Batista
authors.forename: Andrea O
authors.initials: AO
authors.lastname: Magalhães
authors.forename: Philippe
authors.initials: P
authors.lastname: Hawlitschek
authors.forename: Ivone B
authors.initials: IB
authors.lastname: Oliveira
authors.forename: Wagner V
authors.initials: WV
authors.lastname: Dominguez
authors.forename: Rosa M A
authors.initials: RM
authors.lastname: Moysés
authors.forename: Vanda
authors.initials: V
authors.lastname: Jorgetti
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000473:pathology; D005355:Fibrosis / Q000209:etiology* / Q000473:pathology; D007124:Immunoenzyme Techniques; D008297:Male; D009392:Nephrectomy / Q000009:adverse effects; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000378:metabolism*; D016105:Parathyroidectomy / Q000009:adverse effects; D016226:Phosphorus, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014511:Uremia / Q000150:complications* / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D010281:Parathyroid Hormone; D016226:Phosphorus, Dietary