| Full text | |
| Author(s): Show less - |
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 Opportunities: | 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 Opportunities: | 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 Opportunities: | 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 Opportunities: | Scholarships in Brazil - Post-Doctoral |