Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells

Autor: John W. Eaton, Enikő Balogh, Paolo Arosio, György Balla, Maura Poli, Viktória Jeney, Anupam Agarwal, Emese Bányai, Mónika Nyitrai, Katalin Éva Kovács, Ádám Becs, Abolfazl Zarjou, József Balla, Gergely Becs
Rok vydání: 2016
Předmět:
0301 basic medicine
Paricalcitol
β-glycerophosphate
030232 urology & nephrology
Muscle
Smooth
Vascular
chemistry.chemical_compound
0302 clinical medicine
Aorta
Cells
Cultured
Cholecalciferol
Orvostudományok
musculoskeletal system
vascular calcification
Glycerophosphates
Ergocalciferols
cardiovascular system
Osteocalcin
Molecular Medicine
Alkaline phosphatase
Original Article
β‐glycerophosphate
medicine.drug
vitamin D3
medicine.medical_specialty
Calcitriol
Myocytes
Smooth Muscle
chemistry.chemical_element
Thiophenes
Biology
Calcium
ferritin
ferroxidase activity
Klinikai orvostudományok
Phosphates
03 medical and health sciences
Internal medicine
medicine
Humans
Osteoblasts
Thiones
Original Articles
Cell Biology
Alkaline Phosphatase
medicine.disease
Ferritin
030104 developmental biology
Endocrinology
chemistry
Ferritins
biology.protein
Calcification
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
DOI: 10.1111/jcmm.12682
Popis: 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.
Databáze: OpenAIRE
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