Autor(es):Mostrar menos -

Almeida, Youri E. ^[1] ; Fessel, Melissa R. ^[1] ; do Carmo, Luciana Simao ^[1] ; Jorgetti, Vanda ^[2] ; Farias-Silva, Elisangela ^[1] ; Pescatore, Luciana Alves ^{[1, 3]} ; Gamarra, Lionel F. ^[1] ; Andrade, Maria Claudina ^[1] ; Simplicio-Filho, Antonio ^[1] ; Pitangueiras Mangueira, Cristovao Luis ^[1] ; Rangel, Erika B. ^[1] ; Liberman, Marcel ^[1]

Afiliação do(s) autor(es)

^[1] Hosp Israelita Albert Einstein, BR-01425001 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Med Sch, Dept Nephrol, BR-01246000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Hosp Clin, Fac Med, InCor, Lab Biol Vasc, LIM 64, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 JAN 9 2020.
• Citações Web of Science: 0

Resumo

Diabetes mellitus accelerates vascular calcification (VC) and increases the risk of end-stage renal disease (ESRD). Nevertheless, the impact of VC in renal disease progression in type 2 diabetes mellitus (T2DM) is poorly understood. We addressed the effect of VC and mechanisms involved in renal dysfunction in a murine model of insulin resistance and obesity (ob/ob), comparing with their healthy littermates (C57BL/6). We analyzed VC and renal function in both mouse strains after challenging them with Vitamin D-3 (VitD(3)). Although VitD(3) similarly increased serum calcium and induced bone disease in both strains, 24-hour urine volume and creatinine pronouncedly decreased only in ob/ob mice. Moreover, ob/ob increased urinary albumin/creatinine ratio (ACR), indicating kidney dysfunction. In parallel, ob/ob developed extensive intrarenal VC after VitD(3). Coincidently with increased intrarenal vascular mineralization, our results demonstrated that Bone Morphogenetic Protein-2 (BMP-2) was highly expressed in these arteries exclusively in ob/ob. These data depict a greater susceptibility of ob/ob mice to develop renal disease after VitD(3) in comparison to paired C57BL/6. In conclusion, this study unfolds novel mechanisms of progressive renal dysfunction in diabetes mellitus (DM) after VitD(3) in vivo associated with increased intrarenal VC and highlights possible harmful effects of long-term supplementation of VitD(3) in this population. (AU)

• Processo FAPESP: 13/09652-0 - Mecanismos do remodelamento excêntrico associado à calcificação vascular na obesidade e resistência à insulina
• Beneficiário: Luciana Simao Do Carmo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/17961-1 - Investigação do desequilíbrio funcional da proteína glutâmica de matriz na modulação da calcificação vascular em pacientes diabéticos com doença arterial periférica
• Beneficiário: Marcel Liberman
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/09611-2 - Mecanismos do remodelamento excêntrico associado à calcificação vascular na obesidade e resistência à insulina
• Beneficiário: Marcel Liberman
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/25923-0 - Modulação da calcificação vascular pela dissulfeto isomerase proteica (PDI): estudo em um novo modelo de camundongo transgênico
• Beneficiário: Luciana Pescatore Alves
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado