Parathyroid hormone and phosphorus overload in uremia: impact on cardiovascular system

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Custodio, Melani R. ^[1] ; Koike, Marcia K. ^[2] ; Neves, Katia R. ^[1] ; dos Reis, Luciene M. ^[1] ; Graciolli, Fabiana G. ^[1] ; Neves, Carolina L. ^[1] ; Batista, Daniella G. ^[1] ; Magalhaes, Andrea O. ^[1] ; Hawlitschek, Philippe ^[1] ; Oliveira, Ivone B. ^[1] ; Dominguez, Wagner V. ^[1] ; Moyses, Rosa M. A. ^[1] ; Jorgetti, Vanda ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Internal Med, Div Nephrol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Lab Emergency Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Nephrology Dialysis Transplantation; v. 27, n. 4, p. 1437-1445, APR 2012.
• Citações Web of Science: 31

Resumo

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, alpha-actin, transforming growth factor-beta (TGF-beta) 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-beta, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of alpha-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. Conclusion. 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. (AU)

• Processo FAPESP: 01/01789-0 - Avaliacao das alteracoes histologicas osseas e cardiovasculares em ratos uremicos tireoparatireoidectomizados submetidos a dieta rica e pobre em fosforo associada a infusao de paratormonio.
• Beneficiário: Vanda Jorgetti
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/52039-4 - Avaliacao do tecido cardiaco de ratos uremicos paratireodectomizados submetidos a dieta rica e pobre em fosforo associada a infusao de diferentes concentracoes de paratormonio.
• Beneficiário: Vanda Jorgetti
• Modalidade de apoio: Auxílio à Pesquisa - Regular