Sirtuin-1 and Its Relevance in Vascular Calcification

• Published in: International journal of molecular sciences Vol. 21; no. 5; p. 1593
• Main Authors: Lu, Chien-Lin, Liao, Min-Tser, Hou, Yi-Chou, Fang, Yu-Wei, Zheng, Cai-Mei, Liu, Wen-Chih, Chao, Chia-Ter, Lu, Kuo-Cheng, Ng, Yee-Yung
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.02.2020; MDPI
• Subjects: Acetylation; Adipokines; Adiponectin; Adipose tissue; Adipose Tissue - metabolism; Aging; Animals; Antioxidants; Apoptosis; Atherosclerosis; beta Catenin - metabolism; Bioavailability; Biomedical materials; Calciferol; Calcification; Calcification (ectopic); Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - metabolism; Cbfa-1 protein; Cell Transdifferentiation; Cytokines; Deceleration; Diabetes; DNA methylation; Endothelial cells; Endothelial Cells - metabolism; Endothelium; Enzymes; Event-related potentials; Extracellular matrix; Fatty acids; Forkhead Box Protein O1 - metabolism; Forkhead protein; Gene expression; Humans; Hyperphosphatemia; Inflammation; Inflammatory response; Kidney diseases; Kinases; Life span; Liver diseases; Macrophages; Metabolism; Morphology; Muscles; Myocytes, Smooth Muscle - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nitric-oxide synthase; Osteogenesis - physiology; Oxidative stress; perivascular adipose tissue; Proteins; Review; Senescence; Sirtuin 1 - metabolism; sirtuin-1; Smooth muscle; Stiffness; Transcription Factors; Tumor necrosis factor-TNF; vascular calcification; Vascular Calcification - metabolism; Vascular Calcification - prevention & control; vascular smooth muscle cells; Vascular Stiffness; Vitamin D; Vitamin deficiency; perivascular adipose tissue; endothelial cells; sirtuin-1; vascular smooth muscle cells; vascular calcification
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21051593

Vascular calcification (VC) is highly associated with cardiovascular disease and all-cause mortality in patients with chronic kidney disease. Dysregulation of endothelial cells and vascular smooth muscle cells (VSMCs) is related to VC. Sirtuin-1 (Sirt1) deacetylase encompasses a broad range of transcription factors that are linked to an extended lifespan. Sirt1 enhances endothelial NO synthase and upregulates FoxOs to activate its antioxidant properties and delay cell senescence. Sirt1 reverses osteogenic phenotypic transdifferentiation by influencing RUNX2 expression in VSMCs. Low Sirt1 hardly prevents acetylation by p300 and phosphorylation of β-catenin that, following the facilitation of β-catenin translocation, drives osteogenic phenotypic transdifferentiation. Hyperphosphatemia induces VC by osteogenic conversion, apoptosis, and senescence of VSMCs through the Pit-1 cotransporter, which can be retarded by the sirt1 activator resveratrol. Proinflammatory adipocytokines released from dysfunctional perivascular adipose tissue (PVAT) mediate medial calcification and arterial stiffness. Sirt1 ameliorates release of PVAT adipokines and increases adiponectin secretion, which interact with FoxO 1 against oxidative stress and inflammatory arterial insult. Conclusively, Sirt1 decelerates VC by means of influencing endothelial NO bioavailability, senescence of ECs and VSMCs, osteogenic phenotypic transdifferentiation, apoptosis of VSMCs, ECM deposition, and the inflammatory response of PVAT. Factors that aggravate VC include vitamin D deficiency-related macrophage recruitment and further inflammation responses. Supplementation with vitamin D to adequate levels is beneficial in improving PVAT macrophage infiltration and local inflammation, which further prevents VC.