[Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].
Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.
Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Japan.
Masahiko
M
Kurabayashi
D000818:Animals; D002118:Calcium / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000502:physiology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology; D017127:Glycation End Products, Advanced; D006801:Humans; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000235:genetics; D019308:Palmitic Acid; D010758:Phosphorus / Q000502:physiology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D061205:Vascular Calcification / Q000235:genetics* / Q000473:pathology*
D050659:Core Binding Factor Alpha 1 Subunit; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051880:Receptors, Notch; D010758:Phosphorus; D019308:Palmitic Acid; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium