title: [Bone and calcium update; diagnosis and therapy of bone metabolism disease update. Regulatory Mechanism of Mammalian Sirtuin SIRT1 in Vascular calcification: impact of vascular smooth muscle cell senescence].
abstract: Vascular aging manifest several features, namely atherosis, sclerosis and calcified change. Vascular calcification makes the management of hemodynamics more difficult in the elderly, because ectopic calcium deposition in the vasculatures contributes to excessive blood pressure variability, isolated systolic hypertension with increased arterial wave reflectance, and subsequent ischemic cardiovascular (CV) events. Vascular calcification has been shown to result from passive precipitation of calcium with aging and osteoporosis. However, accumulating recent evidences have shown it to be attributable to an active'cell-mediated process'resembling osteogenesis in bone rather than passive mineral precipitation in vascular smooth muscle cells (SMC) . Cellular senescence has been recently shown to be linked to atherosclerogenesis ; however, few reports have addressed whether cellular senescence is associated with SMC calcification. Our new findings show that the senescent phenotypic change is associated with osteoblastic trans-differentiation in SMC and mammalian sirtuin SIRT1, which is well known as a longevity gene, can play an inhibitory role in the cellular senescence-related vascular calcification under hyperphosphatemia. In addition, the activation of Runx2, a potent osteogenic transcriptional factor, in SMC is regulated by SIRT1-p21 axis. The identification of therapeutic targets which can slow down the progression or even reverse the senescent phenotypic change in SMC could be an important step forward in the treatment of vascular calcification.
authors: Department of Geriatric Medicine, The University of Tokyo.
authors: Katsuya
authors: K
authors: Iijima
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology; D016922:Cellular Senescence / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010012:Osteogenesis; D010024:Osteoporosis / Q000209:etiology; D051381:Rats; D056564:Sirtuin 1 / Q000502:physiology*; D061205:Vascular Calcification / Q000209:etiology / Q000235:genetics*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D002118:Calcium