title: The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis.
abstract: Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD+-dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways. Sirt1 expression/activation is decreased in vascular tissue undergoing senescence. Sirt1 deficiency in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and monocytes/macrophages contributes to increased oxidative stress, inflammation, foam cell formation, senescences impaired nitric oxide production and autophagy, thereby promoting vascular aging and atherosclerosis. Endothelial dysfunction, activation of monocytes/macrophages, and the functional and phenotypical plasticity of VSMCs are critically implicated in the pathogenesis of atherosclerosis through multiple mechanisms. Therefore, the activation of Sirt1 in vascular tissue, which includes ECs, monocytes/macrophages and VSMCs, may be a new therapeutic strategy against atherosclerosis and the increasing resistance to the metabolic disorder-related causal factors of CVD. In this review, we discuss the protective role of Sirt1 in the pathophysiology of vascular aging and atherosclerosis.
authors.affiliation: Department of Diabetology and Endocrinology, Kanazawa Medical University. Uchinada, Ishikawa, Japan.|Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors.forename: Munehiro
authors.initials: M
authors.lastname: Kitada
authors.affiliation: Department of Diabetology and Endocrinology, Kanazawa Medical University. Uchinada, Ishikawa, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ogura
authors.affiliation: Department of Diabetology and Endocrinology, Kanazawa Medical University. Uchinada, Ishikawa, Japan.|Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koya
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002319:Cardiovascular System / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D056564:Sirtuin 1
keywords: Sirt1; aging; atherosclerosis; endothelial cell; macrophage