Open AccessPharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells
Author(s) -
Becs Gergely,
Zarjou Abolfazl,
Agarwal Anupam,
Kovács Katalin Éva,
Becs Ádám,
Nyitrai Mónika,
Balogh Enikő,
Bányai Emese,
Eaton John W.,
Arosio Paolo,
Poli Maura,
Jeney Viktória,
Balla József,
Balla György
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12682
Subject(s) - ferritin , calcification , osteocalcin , endocrinology , vascular smooth muscle , medicine , alkaline phosphatase , osteoblast , chemistry , vitamin k2 , matrix gla protein , calcitriol , calcium , vitamin d and neurology , vitamin , biochemistry , ectopic calcification , smooth muscle , in vitro , enzyme
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 D 3 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 D 3 , 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 D 3 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 D 3 caused significantly increased ALP activity in SMC compared to the samples drawn prior to activated vitamin D 3 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.