Ferritin prevents calcification and osteoblastic differentiation of vascular smooth muscle cells

Abolfazl Zarjou, V. Jeney, Paolo Arosio, Maura Poli, Péter Antal-Szalma, Anupam Agarwal, G. Balla, J. Balla

Research output: Contribution to journalArticle

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Abstract

Vascular calcification plays a role in the pathogenesis of atherosclerosis, diabetes, and chronic kidney disease. Human aortic smooth muscle cells (HSMCs) undergo mineralization in response to elevated levels of inorganic phosphate (Pi) in an active and well-regulated process. This process involves increased activity of alkaline phosphatase and increased expression of core binding factor α-1, a bone-specific transcription factor, with the subsequent induction of osteocalcin. Mounting evidence suggests an essential role for the heme oxygenase 1 (HO-1)/ferritin system to maintain homeostasis of vascular function. We examined whether induction of HO-1 and ferritin alters mineralization of HSMCs provoked by high Pi. Upregulation of the HO-1/ferritin system inhibited HSMC calcification and osteoblastic differentiation. Of the products of the system, only ferritin and, to a lesser extent, biliverdin were responsible for the inhibition. Ferritin heavy chain and ceruloplasmin, which both possess ferroxidase activity, inhibited calcification; a site-directed mutant of ferritin heavy chain, which lacked ferroxidase activity, failed to inhibit calcification. In addition, osteoblastic transformation of HSMCs provoked by elevated Pi (assessed by upregulation of core binding factor α-1, osteocalcin, and alkaline phosphatase activity) was diminished by ferritin/ferroxidase activity. We conclude that induction of the HO-1/ferritin system prevents Pi-mediated calcification and osteoblastic differentiation of human smooth muscle cells mainly via the ferroxidase activity of ferritin.

Original languageEnglish
Pages (from-to)1254-1263
Number of pages10
JournalJournal of the American Society of Nephrology
Volume20
Issue number6
DOIs
Publication statusPublished - Jun 2009

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Ferritins
Ceruloplasmin
Vascular Smooth Muscle
Smooth Muscle Myocytes
Heme Oxygenase-1
Core Binding Factors
Apoferritins
Osteocalcin
Alkaline Phosphatase
Up-Regulation
Biliverdine
Vascular Calcification
Chronic Renal Insufficiency
Blood Vessels
Atherosclerosis
Homeostasis
Transcription Factors
Phosphates
Bone and Bones

ASJC Scopus subject areas

  • Nephrology

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Ferritin prevents calcification and osteoblastic differentiation of vascular smooth muscle cells. / Zarjou, Abolfazl; Jeney, V.; Arosio, Paolo; Poli, Maura; Antal-Szalma, Péter; Agarwal, Anupam; Balla, G.; Balla, J.

In: Journal of the American Society of Nephrology, Vol. 20, No. 6, 06.2009, p. 1254-1263.

Research output: Contribution to journalArticle

Zarjou, Abolfazl ; Jeney, V. ; Arosio, Paolo ; Poli, Maura ; Antal-Szalma, Péter ; Agarwal, Anupam ; Balla, G. ; Balla, J. / Ferritin prevents calcification and osteoblastic differentiation of vascular smooth muscle cells. In: Journal of the American Society of Nephrology. 2009 ; Vol. 20, No. 6. pp. 1254-1263.
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