Sirtuin-1 and Its Relevance in Vascular Calcification

被引：73

作者：

Lu, Chien-Lin ^{[1
]}

Liao, Min-Tser ^{[2
,3
,4
]}

Hou, Yi-Chou ^{[4
,5
]}

Fang, Yu-Wei ^{[4
,6
]}

Zheng, Cai-Mei ^{[7
,8
,9
]}

Liu, Wen-Chih ^{[7
,10
]}

Chao, Chia-Ter ^{[11
,12
,13
]}

Lu, Kuo-Cheng ^{[1
]}

Ng, Yee-Yung ^{[1
]}

机构：

[1] Fu Jen Catholic Univ, Fu Jen Catholic Univ Hosp, Sch Med, Div Nephrol,Dept Med, New Taipei 242, Taiwan

[2] Taoyuan Armed Forces Gen Hosp, Dept Pediat, Taoyuan 325, Taiwan

[3] Triserv Gen Hosp, Dept Pediat, Natl Def Med Ctr, Taipei 114, Taiwan

[4] Fu Jen Catholic Univ, Sch Med, Coll Med, New Taipei 24205, Taiwan

[5] Fu Jen Catholic Univ, Sch Med, Cardinal Tien Hosp, Div Nephrol,Dept Med, New Taipei 234, Taiwan

[6] Shin Kong Wu Ho Su Mem Hosp, Div Nephrol, Dept Internal Med, Taipei 111, Taiwan

[7] Taipei Med Univ, Grad Inst Clin Med, Coll Med, Taipei 110, Taiwan

[8] Taipei Med Univ, Sch Med, Div Nephrol, Dept Internal Med,Coll Med, Taipei 110, Taiwan

[9] Taipei Med Univ, Shuang Ho Hosp, Div Nephrol, Dept Internal Med, Taipei 235, Taiwan

[10] Tungs Taichung MetroHarbor Hosp, Div Nephrol, Dept Internal Med, Taichung 433, Taiwan

[11] Natl Taiwan Univ, Grad Inst Toxicol, Coll Med, Taipei 104, Taiwan

[12] Natl Taiwan Univ Hosp, Nephrol Div, Dept Internal Med, Taipei 100, Taiwan

[13] Natl Taiwan Univ Hosp, BeiHu Branch, Dept Internal Med, Taipei 108, Taiwan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 05期

关键词：

sirtuin-1; vascular calcification; endothelial cells; vascular smooth muscle cells; perivascular adipose tissue; SMOOTH-MUSCLE-CELLS; PERIVASCULAR ADIPOSE-TISSUE; VITAMIN-D SUPPLEMENTATION; PHOSPHATE-INDUCED CALCIFICATION; INDUCED PREMATURE SENESCENCE; INHIBITS OXIDATIVE STRESS; NITRIC-OXIDE; ENDOTHELIAL-CELLS; CARDIOVASCULAR-DISEASE; CELLULAR SENESCENCE;

D O I：

10.3390/ijms21051593

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 beta-catenin that, following the facilitation of beta-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.

引用

页数：19

共 147 条

[1]

Calcification of vascular smooth muscle cells is induced by secondary calciprotein particles and enhanced by tumor necrosis factor-α [J].