Expression of mineralisation-regulating proteins in association with human vascular calcification.

Abstract

These studies aim to investigate the expression and function of mineralisation-regulating proteins in association with human vascular calcification focussing on the similarities and differences between the two major calcification pathologies in man: atherosclerotic, intimal calcification and Monckeberg's sclerotic medial calcification. A number of studies have documented expression of mineralisation-regulating proteins in association with human atherosclerotic calcification leading to the suggestion that human vascular calcification may be a regulated process with similarities to developmental osteogenesis. 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 vascular lesions. Additionally, the expression and regulation of bone-associated proteins was analysed during spontaneous calcification of human VSMCs in vitro. In association with both medial and intimal calcification, the temporal changes in expression of mineralisation-regulating proteins are similar. Some constitutively expressed bone-associated proteins, including matrix Gla protein (MGP), are down-regulated in association with calcification while expression of a number of bone-associated proteins, not normally expressed 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 VSMCs while in intimal lesions both VSMCs and macrophages express them. Furthermore, these bone-associated proteins are spontaneously expressed by VSMCs in vitro suggesting that human VSMCs are capable of simultaneously exhibiting smooth muscle and osteogenic-like properties. These studies imply that both medial and intimal vascular calcification are regulated processes; however the aetiology of each pathology differs.