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Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2016 Feb; Vol. 20 (2), pp. 217-30. Date of Electronic Publication: 2015 Oct 26. - Publication Year :
- 2016
-
Abstract
- Vascular calcification is a frequent complication of atherosclerosis, diabetes and chronic kidney disease. In the latter group of patients, calcification is commonly seen in tunica media where smooth muscle cells (SMC) undergo osteoblastic transformation. Risk factors such as elevated phosphorus levels and vitamin D3 analogues have been identified. In the light of earlier observations by our group and others, we sought to inhibit SMC calcification via induction of ferritin. Human aortic SMC were cultured using β-glycerophosphate with activated vitamin D3 , or inorganic phosphate with calcium, and induction of alkaline phosphatase (ALP) and osteocalcin as well as accumulation of calcium were used to monitor osteoblastic transformation. In addition, to examine the role of vitamin D3 analogues, plasma samples from patients on haemodialysis who had received calcitriol or paricalcitol were tested for their tendency to induce calcification of SMC. Addition of exogenous ferritin mitigates the transformation of SMC into osteoblast-like cells. Importantly, pharmacological induction of heavy chain ferritin by 3H-1,2-Dithiole-3-thione was able to inhibit the SMC transition into osteoblast-like cells and calcification of extracellular matrix. Plasma samples collected from patients after the administration of activated vitamin D3 caused significantly increased ALP activity in SMC compared to the samples drawn prior to activated vitamin D3 and here, again induction of ferritin diminished the osteoblastic transformation. Our data suggests that pharmacological induction of ferritin prevents osteoblastic transformation of SMC. Hence, utilization of such agents that will cause enhanced ferritin synthesis may have important clinical applications in prevention of vascular calcification.<br /> (© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
- Subjects :
- Alkaline Phosphatase metabolism
Aorta drug effects
Aorta metabolism
Aorta physiology
Calcitriol metabolism
Calcium metabolism
Cells, Cultured
Cholecalciferol metabolism
Ergocalciferols metabolism
Glycerophosphates pharmacology
Humans
Muscle, Smooth, Vascular drug effects
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular physiology
Myocytes, Smooth Muscle drug effects
Myocytes, Smooth Muscle metabolism
Osteoblasts drug effects
Osteoblasts metabolism
Osteocalcin metabolism
Phosphates metabolism
Thiones pharmacology
Thiophenes pharmacology
Vascular Calcification metabolism
Vascular Calcification physiopathology
Ferritins metabolism
Myocytes, Smooth Muscle physiology
Osteoblasts physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 20
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 26499096
- Full Text :
- https://doi.org/10.1111/jcmm.12682