Expression of mineralisation-regulating proteins in association with humanvascular calcification

Objectives:These studies aim to investigate the expression and function of mineralisation-regulating proteins in association with human vascular calci fication focussing on the similarities and differences between the two majo r calcification pathologies in man: atherosclerotic, intimal calcification and Monckeberg's sclerotic medial calcification. Background: A number of studies have documented expression of mineralisatio n-regulating proteins in association with human atherosclerotic calcificati on leading to the suggestion that human Vascular calcification may be a reg ulated process with similarities to developmental, osteogenesis. Methods: In situ hybridisation, immunohistochemistry and semi-quantitative RT-PCR analysis were used to determine the temporal and spatial expression patterns of mineralisation-regulating proteins within human calcified vascu lar lesions. Additionally, the expression and regulation of bone-associated proteins was analysed during spontaneous calcification of human VSMCs in v itro. Results: In association with both medial and intimal calcification, the tem poral changes in expression of mineralisation-regulating proteins are simil ar. Some constitutively expressed bone-associated proteins, including matri x Gla protein (MGP), are down-regulated in association with calcification w hile expression of a number of bone-associated proteins, not normally expre ssed in the vessel wall, are induced including alkaline phosphatase (ALK), bone sialoprotein (BSP) and bone Gla protein (BGP). In medial calcification the source of expression of these mineralisation-regulating proteins is VS MCs while in intimal lesions both VSMCs and macrophages express them. Furth ermore, these bone-associated proteins are spontaneously expressed by VSMCs in vitro suggesting that human VSMCs are capable of simultaneously exhibit ing smooth muscle and osteogenic-like properties. Conclusions: These studies imply that both medial and intimal vascular calc ification are regulated processes; however the aetiology of each pathology differs.