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Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells

Becs, Gergely and Abolfazl, Zarjou and Agarwal, Anupam and Kovács, Katalin Éva and Becs, Ádám and Nyitrai, Mónika and Balogh, Enikő and Bányai, Emese and Eaton, John W. and Arosio, Paolo and Poli, Maura and Jeney, Viktória and Balla, József and Balla, György (2016) Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE.

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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.

Item Type: Article
Subjects: R Medicine / orvostudomány > RZ Other systems of medicine / orvostudomány egyéb területei
Depositing User: Dr. József Balla
Date Deposited: 13 Sep 2017 17:28
Last Modified: 13 Sep 2017 17:28
URI: http://real.mtak.hu/id/eprint/62376

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