Bone Abstracts

Vascular calcification is a ubiquitous pathology in the aged and diseased vasculature. Recently we have focused on the earliest events in the calcification process and have shown that calcification is initiated in small membrane-bound bodies, or matrix vesicles, derived from both apoptotic and stressed VSMCs. Under normal conditions, these vesicles are loaded with potent inhibitors of mineralization, including matrix Gla protein (MGP) and fetuin-A, which act to block or control crystal nucleation and growth. However, if these proteins are lacking or dysfunctional, or vesicle release is overwhelming calcification ensues. Importantly, using vessels obtained from children with chronic kidney disease (CKD) we have shown that apoptosis and vesicle release, together with dysfunctional inhibitors, are fundamental events in the calcification process in vivo. More recent work has focussed on the mechanisms via which matrix vesicles calcify and we have identified annexins and phosphatidyl serine as important in forming a nucleation complex for the initiation of mineralization. We have also made progress in identifying the sub-cellular origin of VSMC-derived matrix vesicles.

Learning objectives: Vascular calcification is a regulated cell mediated process.

Matrix vesicles are the nucleating factors in vascular calcification.

Extracellular calcium acts to change the mineralization capacity of matrix vesicles.

Matrix vesicles are of endosomal origin and are released as exosomes.