Calcium Overload Accelerates Phosphate-Induced Vascular Calcification Via Pit-1, but not the Calcium-Sensing Receptor
| Autor: | Masaki Ohya, Tomohiro Sonou, Kouji Okuda, Shigeo Negi, Yuri Nakashima, Yuko Iwashita, Toru Mima, Asuka Masumoto, Takashi Shigematsu, Mitsuru Yashiro |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Mönckeberg's arteriosclerosis medicine.medical_specialty Bone metabolism disorder Bone disease Calcimimetic chemistry.chemical_element Phosphate 030204 cardiovascular system & hematology Calcium Phosphates Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Internal medicine Calcium-sensing receptor Internal Medicine medicine Animals Monckeberg's arteriosclerosis Renal Insufficiency Chronic Vascular Calcification Receptor Aorta Chemistry Biochemistry (medical) medicine.disease Rats Pit-1 030104 developmental biology Endocrinology Disease Progression Original Article Transcription Factor Pit-1 Cardiology and Cardiovascular Medicine Receptors Calcium-Sensing Calcification |
| Zdroj: | Journal of Atherosclerosis and Thrombosis |
| ISSN: | 1880-3873 1340-3478 |
| Popis: | Aim: Vascular calcification (VC) is a risk factor of cardiovascular and all-cause mortality in patients with chronic kidney disease (CKD). CKD–mineral and bone metabolism disorder is an important problem in patients with renal failure. Abnormal levels of serum phosphate and calcium affect CKD–mineral and bone metabolism disorder and contribute to bone disease, VC, and cardiovascular disease. Hypercalcemia is a contributing factor in progression of VC in patients with CKD. However, the mechanisms of how calcium promotes intracellular calcification are still unclear. This study aimed to examine the mechanisms underlying calcium-induced calcification in a rat aortic tissue culture model. Methods: Aortic segments from 7-week-old male Sprague–Dawley rats were cultured in serum-supplemented medium for 10 days. We added high calcium (HiCa; calcium 3.0 mM) to high phosphate (HPi; phosphate 3.8 mM) medium to accelerate phosphate and calcium-induced VC. We used phosphonoformic acid and the calcimimetic R-568 to determine whether the mechanism of calcification involves Pit-1 or the calcium-sensing receptor. Results: Medial VC was significantly augmented by HPi+HiCa medium compared with HPi alone (300%, p < 0.05), and was associated with upregulation of Pit-1 protein. Pit-1 protein concentrations in HPi+HiCa medium were greater than those in HPi medium. Phosphonoformic acid completely negated the augmentation of medial VC induced by HPi+HiCa. R-568 had no additive direct effect on medial VC. Conclusion: These results indicated that exposure to HPi+HiCa accelerates medial VC, and this is mediated through Pit-1, not the calcium-sensing receptor. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|