Sirtuin-1 and its relevance in vascular calcification
Journal
International Journal of Molecular Sciences
Journal Volume
21
Journal Issue
5
Pages
1593
Date Issued
2020
Author(s)
Abstract
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. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Endothelial cells; Perivascular adipose tissue; Sirtuin-1; Vascular calcification; Vascular smooth muscle cells
SDGs
Other Subjects
beta catenin; nitric oxide synthase; resveratrol; sirtuin 1; transcription factor Pit 1; transcription factor RUNX2; Wnt protein; adipocytokine; beta catenin; nitric oxide; sirtuin 1; transcription factor; transcription factor FKHR; all cause mortality; antiinflammatory activity; antioxidant activity; apoptosis; arterial stiffness; artery calcification; blood vessel calcification; chronic kidney failure; disease association; enzyme activity; human; hyperphosphatemia; nonhuman; perivascular adipose tissue; phenotype; Review; upregulation; vascular smooth muscle cell; vitamin supplementation; adipose tissue; animal; blood vessel calcification; bone development; cardiovascular disease; cell transdifferentiation; endothelium cell; metabolism; physiology; smooth muscle cell; Adipokines; Adipose Tissue; Animals; Apoptosis; beta Catenin; Cardiovascular Diseases; Cell Transdifferentiation; Endothelial Cells; Forkhead Box Protein O1; Humans; Myocytes, Smooth Muscle; Nitric Oxide; Osteogenesis; Sirtuin 1; Transcription Factors; Vascular Calcification; Vascular Stiffness
Publisher
MDPI AG
Type
review