Article ; Online: Vitamin D Receptor From VSMCs Regulates Vascular Calcification During CKD: A Potential Role for miR-145a.
Arteriosclerosis, thrombosis, and vascular biology
2023 Volume 43, Issue 8, Page(s) 1533–1548
Abstract: Background: Vascular calcification (VC) is a highly prevalent complication of chronic kidney disease (CKD) and is associated with the higher morbidity-mortality of patients with CKD. VDR (vitamin D receptor) has been proposed to play a role in the ... ...
| Abstract | Background: Vascular calcification (VC) is a highly prevalent complication of chronic kidney disease (CKD) and is associated with the higher morbidity-mortality of patients with CKD. VDR (vitamin D receptor) has been proposed to play a role in the osteoblastic differentiation of vascular smooth muscle cells (VSMCs), but the involvement of vitamin D in VC associated to CKD is controversial. Our aim was to determine the role of local vitamin D signaling in VSMCs during CKD-induced VC. Methods: We used epigastric arteries from CKD-affected patients and individuals with normal renal function, alongside an experimental model of CKD-induced VC in mice with conditional deletion of VDR in VSMC. In vitro, experiments in VSMC with or without VDR incubated in calcification media were also used. Results: CKD-affected patients and mice with CKD showed an increase in VC, together with increased arterial expression of VDR compared with controls with normal renal function. Conditional gene silencing of VDR in VSMCs led to a significant decrease of VC in the mouse model of CKD, despite similar levels of renal impairment and serum calcium and phosphate levels. This was accompanied by lower arterial expression of OPN (osteopontin) and lamin A and higher expression of SOST (sclerostin). Furthermore, CKD-affected mice showed a reduction of miR-145a expression in calcified arteries, which was significantly recovered in animals with deletion of VDR in VSMC. In vitro, the absence of VDR prevented VC, inhibited the increase of OPN, and reestablished the expression of miR-145a. Forced expression of miR-145a in vitro in VDR Conclusions: Our study provides evidence proving that inhibition of local VDR signaling in VSMCs could prevent VC in CKD and indicates a possible role for miR-145a in this process. |
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| MeSH term(s) | Mice ; Animals ; Muscle, Smooth, Vascular/metabolism ; Receptors, Calcitriol/genetics ; Vascular Calcification/genetics ; Vascular Calcification/prevention & control ; Kidney/metabolism ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/genetics ; Renal Insufficiency, Chronic/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Vitamin D/metabolism ; Myocytes, Smooth Muscle/metabolism |
| Chemical Substances | Receptors, Calcitriol ; MicroRNAs ; Vitamin D (1406-16-2) |
| Language | English |
| Publishing date | 2023-06-29 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1221433-4 |
| ISSN | 1524-4636 ; 1079-5642 |
| ISSN (online) | 1524-4636 |
| ISSN | 1079-5642 |
| DOI | 10.1161/ATVBAHA.122.318834 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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