PMID- 26995088
OWN - NLM
STAT- MEDLINE
DCOM- 20160921
LR  - 20170802
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 473
IP  - 1
DP  - 2016 Apr 22
TI  - Prolyl hydroxylase 3 overexpression accelerates the progression of 
      atherosclerosis in ApoE-/- mice.
PG  - 99-106
LID - S0006-291X(16)30370-9 [pii]
LID - 10.1016/j.bbrc.2016.03.058 [doi]
AB  - PHD3 belongs to the family of 2-oxoglutarate and iron-dependent dioxygenases and 
      is a critical regulator of HIF-1alpha. Its expression is increased in cardiovascular 
      diseases such as cardiomyopathy, myocardial ischemia-reperfusion injury, and 
      congestive heart failure. However, the association between PHD3 and 
      atherosclerosis has not been clearly elucidated. In the present study, we 
      investigated the potential effect and mechanism of PHD3 in apolipoprotein 
      E-deficient (ApoE-/-) mice. Murine PHD3 lentivirus and shRNA -PHD3 lentivirus 
      were constructed and injected intravenously into ApoE-/- mice fed on a high fat 
      diet. The aortic atherosclerotic lesion area was larger with PHD3 
      over-expression. With increased PHD3 levels, macrophages and smooth muscle cells 
      were enhanced. The apoptosis of atherosclerotic plaques revealed an increase when 
      PHD3 was elevated. Furthermore, the expression of intercellular cell adhesion 
      molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), monocyte 
      chemotactic protein 1 (MCP-1), interleukin-1beta (IL-1beta) and tumor necrosis 
      factor-alpha(TNF-alpha) were upregulated with PHD3 over-expression. In vitro, we explored 
      the specific signaling pathway of PHD3 in HUVECs. PHD3 over-expression is 
      associated with activation of ERK1/2 and JNK phosphorylation of MAPK signaling 
      pathway. PHD3 inhibition decreased the apoptosis of HUVECs treated with ox-LDL 
      (50 mug/ml). Our study suggests that PHD3 is not only a regulator of HIF-1alpha but 
      also an active participant in atherogenesis.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Liu, Hui
AU  - Liu H
AD  - Qilu Hospital of Shandong University, The Key Laboratory of Cardiovascular 
      Remodeling and Function Research, Chinese Ministry of Education and Chinese 
      Ministry of Public Health, Jinan, Shandong 250012, China.
FAU - Xia, Yanfei
AU  - Xia Y
AD  - Qilu Hospital of Shandong University, The Key Laboratory of Cardiovascular 
      Remodeling and Function Research, Chinese Ministry of Education and Chinese 
      Ministry of Public Health, Jinan, Shandong 250012, China.
FAU - Li, Beibei
AU  - Li B
AD  - Qilu Hospital of Shandong University, The Key Laboratory of Cardiovascular 
      Remodeling and Function Research, Chinese Ministry of Education and Chinese 
      Ministry of Public Health, Jinan, Shandong 250012, China.
FAU - Pan, Jinyu
AU  - Pan J
AD  - Qilu Hospital of Shandong University, The Key Laboratory of Cardiovascular 
      Remodeling and Function Research, Chinese Ministry of Education and Chinese 
      Ministry of Public Health, Jinan, Shandong 250012, China.
FAU - Lv, Mei
AU  - Lv M
AD  - Qilu Hospital of Shandong University, The Key Laboratory of Cardiovascular 
      Remodeling and Function Research, Chinese Ministry of Education and Chinese 
      Ministry of Public Health, Jinan, Shandong 250012, China.
FAU - Wang, Xuyang
AU  - Wang X
AD  - Qilu Hospital of Shandong University, The Key Laboratory of Cardiovascular 
      Remodeling and Function Research, Chinese Ministry of Education and Chinese 
      Ministry of Public Health, Jinan, Shandong 250012, China.
FAU - An, Fengshuang
AU  - An F
AD  - Qilu Hospital of Shandong University, The Key Laboratory of Cardiovascular 
      Remodeling and Function Research, Chinese Ministry of Education and Chinese 
      Ministry of Public Health, Jinan, Shandong 250012, China. Electronic address: 
      anfengshuang1028@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160316
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Apolipoproteins E)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (ICAM1 protein, human)
RN  - 0 (IL1B protein, human)
RN  - 0 (IL1B protein, mouse)
RN  - 0 (Icam1 protein, mouse)
RN  - 0 (Interleukin-1beta)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 1.14.11.2 (PHD3 protein, mouse)
RN  - EC 1.14.11.2 (Procollagen-Proline Dioxygenase)
SB  - IM
MH  - Animals
MH  - Aorta/pathology
MH  - Apolipoproteins E/*genetics
MH  - Apoptosis
MH  - Atherosclerosis/*genetics/metabolism/pathology
MH  - Chemokine CCL2/metabolism
MH  - Disease Progression
MH  - *Gene Expression Regulation
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Inflammation
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Interleukin-1beta/metabolism
MH  - MAP Kinase Signaling System
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Procollagen-Proline Dioxygenase/*genetics/*metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Vascular Cell Adhesion Molecule-1/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Atherosclerosis
OT  - MAPK
OT  - Prolyl hydroxylase 3
EDAT- 2016/03/21 06:00
MHDA- 2016/09/23 06:00
CRDT- 2016/03/21 06:00
PHST- 2016/03/12 00:00 [received]
PHST- 2016/03/15 00:00 [accepted]
PHST- 2016/03/21 06:00 [entrez]
PHST- 2016/03/21 06:00 [pubmed]
PHST- 2016/09/23 06:00 [medline]
AID - S0006-291X(16)30370-9 [pii]
AID - 10.1016/j.bbrc.2016.03.058 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2016 Apr 22;473(1):99-106. doi: 
      10.1016/j.bbrc.2016.03.058. Epub 2016 Mar 16.