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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Excessive cholecalciferol supplementation increases kidney dysfunction associated with intrarenal artery calcification in obese insulin-resistant mice

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Author(s):
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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]
Total Authors: 12
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 10, n. 1 JAN 9 2020.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 13/09652-0 - Mechanisms of excentric remodeling associated with vascular calcification in obesity and insulin resistance
Grantee:Luciana Simao Do Carmo
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 16/17961-1 - Role of gamma-carboxyglutamic protein functional imbalance in vascular calcification modulation of diabetic patients with peripheral arterial disease
Grantee:Marcel Liberman
Support type: Regular Research Grants
FAPESP's process: 13/09611-2 - Mechanisms of excentric remodeling associated with vascular calcification in obesity and insulin resistance
Grantee:Marcel Liberman
Support type: Regular Research Grants
FAPESP's process: 15/25923-0 - Modulation of vascular calcification by protein disulfide isomerase: study on a new transgenic mouse model
Grantee:Luciana Pescatore Alves
Support type: Scholarships in Brazil - Post-Doctorate