Mechanism of atherosclerotic calcification

Calcification is almost invariably associated with atherosclerotic plaque l esions. Recent data suggest that plaque calcification is an active, regulat ed process similar to osteogenesis. In order to clarify the mechanism of pl aque calcification, we developed an in vitro model of vascular calcificatio n by utilizing bovine vascular smooth muscle cells (BVSMCs). This model is useful in that diffuse and massive calcification can be induced within 2 we eks and thereby biochemical analyses of vascular calcification can be perfo rmed. We have analyzed several aspects of vascular calcification by using t his model and demonstrated as follows: 1) in vitro calcification of BVSMCs is regulated by calciotropic hormones and BVSMCs are equipped with a unique autocrine and/or paracrine system regulating calcium metabolism. 2) Sodium -dependent phosphate cotransport plays a crucial role in BVSMC calcificatio n as well as in mineralization of skeletal tissues. 3) BVSMCs acquire osteo blastic phenotype under certain conditions. Finally, we discuss the roles o f macrophages in the development of atherosclerotic calcification. Interfer on-gamma (IFN-gamma) induces gene expression of 25-hydrovitamin D-1 alpha-h ydroxylase (1 alpha OHase) and its activity in macrophages. Since 1 alpha O Hase can locally convert 25-hydroxyvitamin D into 1 alpha,25-dihydroxyvitam in D (1,25(OH)(2)D), an active metabolite of vitamin D, it is suggested tha t local production of 1,25(OH)(2)D by macrophages may promote atherosclerot ic calcification. Moreover, macrophages may be involved in the phenotypic c hanges of vascular smooth muscle cells (VSMCs) to acquire calcifying capaci ty. Therefore, the phenotypic changes of VSMCs in atherosclerotic plaque ma y contribute to the development of atherosclerotic calcification.