PMID- 28024939
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20181126
IS  - 0925-4439 (Print)
IS  - 0925-4439 (Linking)
VI  - 1863
IP  - 3
DP  - 2017 Mar
TI  - RAGE deficiency alleviates aortic valve calcification in ApoE(-/-) mice via the 
      inhibition of endoplasmic reticulum stress.
PG  - 781-792
LID - S0925-4439(16)30349-0 [pii]
LID - 10.1016/j.bbadis.2016.12.012 [doi]
AB  - Receptor for advanced glycation end products (RAGE) and endoplasmic reticulum 
      (ER) stress have been shown to be involved in calcific aortic valve disease 
      (CAVD). However, the association between RAGE and ER stress remains unknown in 
      the pathogenesis of CAVD. The current study aims to test the hypothesis that RAGE 
      deficiency alleviates aortic valve calcification via the inhibition of ER stress. 
      Up-regulation of RAGE and ER stress markers in calcified human aortic valves were 
      confirmed by immunoblotting. Aortic valve calcification was evaluated in 
      atherosclerotic prone ApoE(-/-) mice or in mice with dual deficiencies of ApoE 
      and RAGE (ApoE(-/-)RAGE(-/-)) fed with high cholesterol diet for 24weeks. 
      Echocardiography and histological examination show that genetic deficiency of 
      RAGE attenuates aortic valve calcification in ApoE(-/-) mice. Meanwhile, RAGE 
      deficiency inhibited the osteogenic signaling and ER stress activation as well as 
      suppressed macrophage infiltration in vivo. Cultured human aortic valve 
      interstitial cells (AVICs) were treated with high molecular group box 1 protein 
      (HMGB1) as in vitro model. We found that HMGB1 induced osteoblastic 
      differentiation and calcification through RAGE/ER stress. Furthermore, Sox9 
      up-regulation and intranuclear translocation mediated the pro-osteogenic effect 
      of HMGB1 on AVICs. RAGE or ER stress knockdown reduced the up-regulation of 
      monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in 
      human AVICs exposed to HMGB1.These novel findings demonstrate that RAGE 
      deficiency protects against aortic valve calcification in high cholesterol 
      diet-fed ApoE(-/-) mice via inhibition of ER stress. HMGB1 induces AVIC 
      osteoblastic differentiation and calcification through RAGE/ER stress/Sox9 
      pathway.
CI  - Copyright (c) 2016. Published by Elsevier B.V.
FAU - Wang, Bo
AU  - Wang B
AD  - Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 
      430060, China.
FAU - Cai, Zhejun
AU  - Cai Z
AD  - Department of Cardiology, Second Affiliated Hospital, College of Medicine, 
      Zhejiang University, Hangzhou, Zhejiang 310009, China.
FAU - Liu, Baoqing
AU  - Liu B
AD  - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
FAU - Liu, Zongtao
AU  - Liu Z
AD  - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
FAU - Zhou, Xianming
AU  - Zhou X
AD  - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
FAU - Dong, Nianguo
AU  - Dong N
AD  - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. 
      Electronic address: dongnianguo@hotmail.com.
FAU - Li, Fei
AU  - Li F
AD  - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. 
      Electronic address: lifei_union@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161224
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - 0 (Apolipoproteins E)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - Aortic Valve, Calcification of
SB  - IM
MH  - Animals
MH  - Aortic Valve/metabolism/*pathology
MH  - Aortic Valve Stenosis/*genetics/metabolism/*pathology
MH  - Apolipoproteins E/*genetics/metabolism
MH  - Calcinosis/*genetics/metabolism/*pathology
MH  - Cells, Cultured
MH  - Cholesterol/metabolism
MH  - *Endoplasmic Reticulum Stress
MH  - *Gene Deletion
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptor for Advanced Glycation End Products/*genetics/metabolism
OTO - NOTNLM
OT  - Aortic valve calcification
OT  - ER stress
OT  - HMGB1
OT  - RAGE
OT  - Sox9
EDAT- 2016/12/28 06:00
MHDA- 2018/11/27 06:00
CRDT- 2016/12/28 06:00
PHST- 2016/08/11 00:00 [received]
PHST- 2016/12/22 00:00 [revised]
PHST- 2016/12/23 00:00 [accepted]
PHST- 2016/12/28 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2016/12/28 06:00 [entrez]
AID - S0925-4439(16)30349-0 [pii]
AID - 10.1016/j.bbadis.2016.12.012 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Basis Dis. 2017 Mar;1863(3):781-792. doi: 
      10.1016/j.bbadis.2016.12.012. Epub 2016 Dec 24.