Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 29, Issue 5, Pages 761-U303Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.108.183384
Keywords
phosphonoformic acid; bisphosphonate; vascular calcification; phosphate transport; Pit-1
Categories
Funding
- Spanish Ministry of Education and Science [BFU2006-06284/BFI]
- Government of Aragon, Spain [B086/2007]
Ask authors/readers for more resources
Objective-The role of inorganic phosphate in the pathogenesis of vascular calcification ( VC) has been studied extensively in recent years. Phosphonoformic acid (PFA), an inhibitor of type II Pi transporters, has been traditionally used to study the involvement of Pi transport in VC, because PFA also prevents calcium deposition in vitro. However, aortic vascular smooth muscle cells (VSMCs) only express PFA-resistant, type III transporters (Pit-1 and Pit-2). Therefore, in this article we have studied the mechanism of VC prevention by PFA. Methods and Results-Radiotracer Pi uptake in rat VSMCs was not inhibited at the concentrations at which PFA prevents calcification. Alternative mechanisms whereby PFA could prevent calcification, such as cytotoxicity or phosphodiesterase inhibition, have also been excluded. The progression of calcification also took place in fixed cells. The kinetics of VC prevention by PFA, pyrophosphate, phosphonoacetate, and bisphosphonates was similar in live and fixed cells, showing mean effective concentrations in the micromolar range. Conclusions-PFA mainly prevents VC through a physicochemical mechanism that is independent of any cellular metabolic activity, including Pi transport. Conversely, PFA seems to act similarly to its chemical analogues, inorganic pyrophosphate, and bisphosphonates, as suggested decades ago. (Arterioscler Thromb Vasc Biol. 2009; 29: 761-766.)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available