PMID- 31401381
OWN - NLM
STAT- MEDLINE
DCOM- 20200213
LR  - 20200213
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 75
DP  - 2019 Oct
TI  - Sitagliptin inhibits vascular inflammation via the SIRT6-dependent signaling 
      pathway.
PG  - 105805
LID - S1567-5769(19)30110-9 [pii]
LID - 10.1016/j.intimp.2019.105805 [doi]
AB  - Sitagliptin has recently been shown to inhibit inflammatory response in 
      cardiovascular disease. Sirtuin6 (SIRT6), a NAD(+)-dependent class III histone 
      deacetylase, participates in the regulation of cellular inflammation. We 
      hypothesized that sitagliptin could attenuate vascular inflammation via 
      modulation of SIRT6 pathway. It was found that sitagliptin decreased the 
      expression of monocyte chemotactic protein-1 (MCP-1), interleukin (IL)-6 and 
      IL-1beta, but up-regulated SIRT6 expression, both in mice and in TNF-alpha-stimulated 
      endothelial cells. Moreover, knockdown of SIRT6 reversed the inhibitory effect of 
      sitagliptin on MCP-1, IL-6 and IL-1beta expression. Further study revealed that 
      sitagliptin also decreased the expression of MCP-1, IL-6 and IL-1beta partly through 
      suppression of reactive oxygen species (ROS). In vivo, hypercholesterolemia in 
      mice was induced by intraperitoneal administration of poloxamer 407 for 1 month. 
      Hyperlipidemia-induced production of MCP-1, IL-6 and IL-1beta was significantly 
      suppressed in the sitagliptin-supplemented animals, but the effect of was 
      abolished by SIRT6 knockout in endothelium. These results indicate that 
      sitagliptin protects against vascular inflammation via the SIRT6/ROS-dependent 
      signaling pathway.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - He, Yanhao
AU  - He Y
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Yang, Guangde
AU  - Yang G
AD  - School of Pharmacy, Xi'an Jiaotong University, Health Science Center, Xi'an, 
      Shaanxi 710061, China.
FAU - Yao, Feng
AU  - Yao F
AD  - School of Pharmacy, Xi'an Jiaotong University, Health Science Center, Xi'an, 
      Shaanxi 710061, China.
FAU - Xian, Yushan
AU  - Xian Y
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Wang, Guan
AU  - Wang G
AD  - School of Pharmacy, Xi'an Jiaotong University, Health Science Center, Xi'an, 
      Shaanxi 710061, China.
FAU - Chen, Lifang
AU  - Chen L
AD  - Laboratory Animal Center, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Lv, Xiaohan
AU  - Lv X
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Gao, Hongqian
AU  - Gao H
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Zheng, Zihan
AU  - Zheng Z
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Sun, Lijing
AU  - Sun L
AD  - Department of Pharmacy, Second Affiliated Hospital of Xi'an Jiaotong University, 
      Xi'an, Shaanxi 710004, China.
FAU - Wang, Weirong
AU  - Wang W
AD  - Laboratory Animal Center, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Lin, Rong
AU  - Lin R
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China. Electronic address: linrong63@aliyun.com.
LA  - eng
PT  - Journal Article
DEP - 20190808
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.4.2.31 (Sirt6 protein, mouse)
RN  - EC 3.5.1.- (Sirtuins)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Aorta/drug effects/metabolism
MH  - Cell Line
MH  - Cytokines/genetics/metabolism
MH  - Endothelial Cells/drug effects/metabolism
MH  - Endothelium, Vascular/*drug effects/metabolism
MH  - Humans
MH  - Hypercholesterolemia/chemically induced/metabolism
MH  - Mice, Transgenic
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirtuins/*genetics
MH  - Sitagliptin Phosphate/*pharmacology
OTO - NOTNLM
OT  - Inflammation
OT  - ROS
OT  - SIRT6
OT  - Sitagliptin
EDAT- 2019/08/12 06:00
MHDA- 2020/02/14 06:00
CRDT- 2019/08/12 06:00
PHST- 2019/01/20 00:00 [received]
PHST- 2019/08/01 00:00 [revised]
PHST- 2019/08/01 00:00 [accepted]
PHST- 2019/08/12 06:00 [pubmed]
PHST- 2020/02/14 06:00 [medline]
PHST- 2019/08/12 06:00 [entrez]
AID - S1567-5769(19)30110-9 [pii]
AID - 10.1016/j.intimp.2019.105805 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2019 Oct;75:105805. doi: 10.1016/j.intimp.2019.105805. Epub 
      2019 Aug 8.