Mechanism of atherosclerotic calcification.
Calcification is almost invariably associated with atherosclerotic plaque lesions. Recent data suggest that plaque calcification is an active, regulated process similar to osteogenesis. In order to clarify the mechanism of plaque calcification, we developed an in vitro model of vascular calcification by utilizing bovine vascular smooth muscle cells (BVSMCs). This model is useful in that diffuse and massive calcification can be induced within 2 weeks and thereby biochemical analyses of vascular calcification can be performed. We have analyzed several aspects of vascular calcification by using this 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 calcification as well as in mineralization of skeletal tissues. 3) BVSMCs acquire osteoblastic phenotype under certain conditions. Finally, we discuss the roles of macrophages in the development of atherosclerotic calcification. Interferon-gamma (IFN-gamma) induces gene expression of 25-hydrovitamin D-1 alpha-hydroxylase (1 alpha OHase) and its activity in macrophages. Since 1 alpha OHase can locally convert 25-hydroxyvitamin D into 1 alpha, 25-dihydroxyvitamin D (1,25(OH)2D), an active metabolite of vitamin D, it is suggested that local production of 1,25(OH)2D by macrophages may promote atherosclerotic calcification. Moreover, macrophages may be involved in the phenotypic changes of vascular smooth muscle cells (VSMCs) to acquire calcifying capacity. Therefore, the phenotypic changes of VSMCs in atherosclerotic plaque may contribute to the development of atherosclerotic calcification.
Shioi
A
A
Department of Cardiovascular Medicine, Osaka City University Medical School, Japan. as@msic.med.osaka-cu.ac.jp
Mori
K
K
Jono
S
S
Wakikawa
T
T
Hiura
Y
Y
Koyama
H
H
Okuno
Y
Y
Nishizawa
Y
Y
Morii
H
H
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D002114:Calcinosis / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D046508:Culture Techniques; D006801:Humans; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology; D010012:Osteogenesis / Q000502:physiology
D002118:Calcium