Daily peritoneal administration of sodium pyrophosphate in a dialysis solution prevents the development of vascular calcification in a mouse model of uraemia.
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Activation of receptor for advanced glycation end products induces osteogenic differentiation of vascular smooth muscle cells.
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AIM: Vascular calcification is prevalent in patients with diabetes and chronic kidney disease. Receptor for advanced glycation end products (RAGE) and its multiple ligands have been implicated in the pathogenesis of accelerated atherosclerosis; however, little is known about the effects of RAGE activation on vascular calcification. METHODS AND RESULTS: Cultured rat and human aortic smooth muscle cells (HASMC) were transduced with adenovirus expressing RAGE. Expression of myocardin and the SMC-marker genes was significantly repressed in these cells. RAGE activation inhibited myocardin-induced expression of the SMC genes in mouse embryonic mesenchymal C3H10T1/2 cells. Interestingly, RAGE activation induced alkaline phosphatase (ALP) expression, calcium deposition, and Msx2 expression, a crucial transcription factor for osteogenic differentiation, in HASMC. RAGE-induced osteogenic differentiation was significantly inhibited by endogenous secretory RAGE. RAGE-induced ALP and Msx2 expression was completely abrogated by DAPT, an inhibitor of the Notch signaling pathway. PD98059 (MEK inhibitor) effectively blunted RAGE-induced Notch1 and Msx2 gene expression. Simultaneous stimulation with bone morphogenetic protein 2 (BMP2) and RAGE signaling synergistically induced expressions of Msx2 and ALP in HASMC. Immunohistochemistry revealed that the human calcifying atherosclerotic plaque expressed RAGE, Notch components and Msx2. The ALP activity induced in RAGE-overexpressing HASMCs by human serum was positively correlated with the serum creatinine level, but not with phosphate and hemoglobin A1c levels. CONCLUSIONS: These results indicate that activation of RAGE not only inhibits myocardin-dependent SMC gene expression, but also induces osteogenic differentiation of vascular SMC through Notch/Msx2 induction. These results provide a novel insight into the role of RAGE axis in vascular calcification. (+info)
Ankle--brachial index, vascular calcifications and mortality in dialysis patients.
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Osteo-progenitors in vascular calcification: a circulating cell theory.
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Vascular calcification has been associated with the incidence of cardiovascular events and thus there has been interest in better understanding its pathogenesis. Early theories considered vascular calcification to be a passive process which occurred as a non-specific response to tissue injury or necrosis. More recent theories propose vascular calcification results from loss of molecular inhibitors or via an active cell mediated process. The origin of the cells responsible for vascular calcification is controversial and may vary in different sites and patients. Calcification has been reported as result of apoptosis or death of vascular smooth muscle cells for example. One novel source of cells controlling vascular calcification is from the bone marrow. A circulating immature bone marrow derived population has been identified and a small subset of this bone marrow population has been reported to possess bone forming properties in vitro and hence termed osteo-progenitors. This article reviews evidence supporting the contribution of these naive bone marrow derived circulating osteo-progenitor cells in vascular calcification. (+info)
Lack of association of Klotho gene variants with valvular and vascular calcification in Caucasians: a candidate gene study of the Framingham Offspring Cohort.
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