Vascular calcification plays a role in the pathogenesis of atherosclerosis, diabetes and chronic kidney disease. The mechanism of vascular calcification is not completely understood, but recent evidence implicates factors involved in bone mineralization. In response to elevated inorganic phosphate transdifferentiation of vascular smooth muscle cells (VSMC) into osteoblast-like cells occurs. This process involves increased alkaline phosphatase activity, increased expression of the bone specific transcription factor, core binding factor-1, and the subsequent induction of osteocalcin. Mounting evidence suggests an essential role for ferritin to maintain homeostasis of vascular function. Recently we have found that both exogenous administration of ferritin and upregulation of endogenous ferritin production inhibit calcification and transdifferentiation of VSMC. Ferritin is a multifunctional protein, possessing ferroxidase activity and iron storing ability. In addition, as recently described, ferritin plays a role in transcriptional regulation of certain genes. Testing the inhibitory potential of different ferritins - L-ferritin, H-ferritin and a mutant form of H-ferritin lacking ferroxidase activity - revealed that ferroxidase activity of ferritin is essential to dampen Pi-induced calcification. Moreover, we have found that ceruloplasmin, a distinct protein with ferroxidase activity inhibited calcification and osteoblastic transdifferentiation of VSMC. In addition, we have shown that ferritin - via its ferroxidase activity - inhibits osteoblast activity, leading to decreased mineralization. These results suggest a novel role of ferritin/ferroxidase activity in inhibiting vascular calcification, VSMC-osteoblast transformation, osteoblast activity and mineralization.
|Title of host publication||Ferritin|
|Subtitle of host publication||Functions, Biosynthesis and Regulation|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||18|
|Publication status||Published - Dec 1 2012|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)