PMID- 27831589
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20180323
IS  - 2567-689X (Electronic)
IS  - 0340-6245 (Linking)
VI  - 117
IP  - 2
DP  - 2017 Jan 26
TI  - The anti-inflammatory vasostatin-2 attenuates atherosclerosis in ApoE(-/-) mice 
      and inhibits monocyte/macrophage recruitment.
PG  - 401-414
LID - 10.1160/TH16-06-0475 [doi]
AB  - We showed previously that reduced level of vasostatin-2 (VS-2) correlates to the 
      presence and severity of coronary artery disease. In this study, we aimed to 
      figure out the role of chromogranin A (CGA) derived VS-2 in the development of 
      atherosclerosis and monocyte/macrophage recruitment. Apolipoprotein E-deficient 
      (ApoE(-/-)) mice fed a high-fat diet exhibited attenuated lesion size by 65 % and 
      41 % in En face and aortic root Oil red O staining, MOMA-2 positive area by 64 %, 
      respectively, in VS-2 treatment group compared with PBS group. Proinflammatory 
      cytokines tumour necrosis factor-alpha (TNF-alpha), monocyte chemoattractant 
      protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) were all 
      remarkably reduced in aortic tissues after VS-2 treatment. Mechanistically, in 
      adhesion assay using intravital microscopy in vivo, VS-2 suppressed the number of 
      leukocytes adhering to the wall of apoE(-/-) mice mesenteric arteries. In 
      chemotactic assay, flow cytometry analysis of peritoneal lavage exudate from 
      C57BL/6 mice showed VS-2 significantly decreased the recruiment number of 
      inflammatory monocytes/macrophages in a thioglycollate-induced peritonitis model. 
      Furthermore, fewer fluorescent latex beads labelled Ly-6C(hi) monocytes 
      accumulated in aortic sinus lesions of apoE(-/-) mice after VS-2 treatment. In 
      addition, according to the microarray of human monocyte/macrophage, we found VS-2 
      stimulation caused a dose-dependent decrease of Rac1 expression and inactivation 
      of Pak1 in mice primary monocytes as well as THP-1 cells and inhibited 
      MCP-1/CCL-5 induced transmigration in vitro. In conclusion, the Chromogranin 
      A-derived VS-2 attenuates atherosclerosis in apoE(-/-) mice and, in addition to 
      its anti-inflammatory property, also acts as an inhibitor in monocyte/macrophage 
      recruitment.
FAU - Xiong, Weixin
AU  - Xiong W
FAU - Wang, Xiaoqun
AU  - Wang X
FAU - Dai, Daopeng
AU  - Dai D
FAU - Zhang, Bao
AU  - Zhang B
FAU - Lu, Lin
AU  - Lu L
AD  - Lin Lu, Department of Cardiology, Ruijin Hospital, Jiao Tong University School of 
      Medicine, Shanghai 200025, P. R. China, Tel.: +86 21 64370045, Fax: +86 21 
      64457177, E-mail: rjlulin1965@163.com.
FAU - Tao, Rong
AU  - Tao R
AD  - Rong Tao, Department of Cardiology, Ruijin Hospital, Jiao Tong University School 
      of Medicine, Shanghai 200025, P. R. China, Tel.: +86 21 64370045, Fax: +86 21 
      64457177, E-mail: rongtao@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161110
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chromogranin A)
RN  - 0 (Neuropeptides)
RN  - 0 (Peptide Fragments)
RN  - 0 (Rac1 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 162164-15-0 (vasostatin II)
RN  - EC 2.7.11.1 (Pak1 protein, mouse)
RN  - EC 2.7.11.1 (p21-Activated Kinases)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Actin Cytoskeleton/drug effects/metabolism
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Aorta/*drug effects/metabolism/pathology
MH  - Aortic Diseases/genetics/metabolism/pathology/*prevention & control
MH  - Atherosclerosis/genetics/metabolism/pathology/*prevention & control
MH  - Cell Adhesion/drug effects
MH  - Chemokine CCL2/metabolism
MH  - Chemotaxis, Leukocyte/drug effects
MH  - Chromogranin A/*pharmacology
MH  - Coculture Techniques
MH  - Diet, High-Fat
MH  - Disease Models, Animal
MH  - Human Umbilical Vein Endothelial Cells/drug effects/metabolism/pathology
MH  - Humans
MH  - Inflammation/genetics/metabolism/pathology/*prevention & control
MH  - Macrophages/*drug effects/metabolism/pathology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout, ApoE
MH  - Monocytes/*drug effects/metabolism/pathology
MH  - Neuropeptides/metabolism
MH  - Peptide Fragments/*pharmacology
MH  - Plaque, Atherosclerotic
MH  - Signal Transduction/drug effects
MH  - THP-1 Cells
MH  - Transendothelial and Transepithelial Migration/drug effects
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - U937 Cells
MH  - Vascular Cell Adhesion Molecule-1/metabolism
MH  - p21-Activated Kinases/metabolism
MH  - rac1 GTP-Binding Protein/metabolism
OTO - NOTNLM
OT  - Atherosclerosis
OT  - chemotaxis
OT  - inflammation
OT  - monocytes
OT  - vasostatin-2
EDAT- 2016/11/11 06:00
MHDA- 2018/02/27 06:00
CRDT- 2016/11/11 06:00
PHST- 2016/06/27 00:00 [received]
PHST- 2016/10/18 00:00 [accepted]
PHST- 2016/11/11 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2016/11/11 06:00 [entrez]
AID - 16-06-0475 [pii]
AID - 10.1160/TH16-06-0475 [doi]
PST - ppublish
SO  - Thromb Haemost. 2017 Jan 26;117(2):401-414. doi: 10.1160/TH16-06-0475. Epub 2016 
      Nov 10.