PMID- 29420219
OWN - NLM
STAT- MEDLINE
DCOM- 20191210
LR  - 20240314
IS  - 2047-9980 (Electronic)
IS  - 2047-9980 (Linking)
VI  - 7
IP  - 3
DP  - 2018 Feb 2
TI  - Neopterin Counters Vascular Inflammation and Atherosclerosis.
LID - 10.1161/JAHA.117.007359 [doi]
LID - e007359
AB  - BACKGROUND: Neopterin, a metabolite of GTP, is produced by activated macrophages 
      and is abundantly expressed within atherosclerotic lesions in human aorta and 
      carotid and coronary arteries. We aimed to clarify the influence of neopterin on 
      both vascular inflammation and atherosclerosis, as neither effect had been fully 
      assessed. METHODS AND RESULTS: We investigated neopterin expression in coronary 
      artery lesions and plasma from patients with coronary artery disease. We assessed 
      the atheroprotective effects of neopterin in vitro using human aortic endothelial 
      cells, human monocyte-derived macrophages, and human aortic smooth muscle cells. 
      In vivo experiments included a study of aortic lesions in apolipoprotein 
      E-deficient mice. Neopterin expression in coronary artery lesions and plasma was 
      markedly increased in patients with versus without coronary artery disease. In 
      human aortic endothelial cells, neopterin reduced proliferation and TNF-alpha (tumor 
      necrosis factor alpha)-induced upregulation of MCP-1 (monocyte chemotactic protein 
      1), ICAM-1 (intercellular adhesion molecule 1), and VCAM-1 (vascular cell 
      adhesion molecule 1). Neopterin attenuated TNF-alpha-induced monocyte adhesion to 
      human aortic endothelial cells and the inflammatory macrophage phenotype via 
      NF-kappaB (nuclear factor-kappaB) downregulation. Neopterin suppressed oxidized 
      low-density lipoprotein-induced foam cell formation associated with CD36 
      downregulation and upregulation of ATP-binding cassette transporters A1 and G1 in 
      human monocyte-derived macrophages. In human aortic smooth muscle cells, 
      neopterin suppressed angiotensin II-induced migration and proliferation via 
      c-Src/Raf-1/ERK1/2 downregulation without inducing apoptosis. Exogenous neopterin 
      administration and endogenous neopterin attenuation with its neutralizing 
      antibody for 4 weeks retarded and promoted, respectively, the development of 
      aortic atherosclerotic lesions in apolipoprotein E-deficient mice. CONCLUSIONS: 
      Our results indicate that neopterin prevents both vascular inflammation and 
      atherosclerosis and may be induced to counteract the progression of 
      atherosclerotic lesions. Consequently, neopterin could be of use as a novel 
      therapeutic target for atherosclerotic cardiovascular diseases.
CI  - (c) 2018 The Authors. Published on behalf of the American Heart Association, Inc., 
      by Wiley.
FAU - Shirai, Remina
AU  - Shirai R
AD  - Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo, Japan.
FAU - Sato, Kengo
AU  - Sato K
AD  - Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo, Japan ksato@toyaku.ac.jp.
FAU - Yamashita, Tomoyuki
AU  - Yamashita T
AD  - Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo, Japan.
FAU - Yamaguchi, Maho
AU  - Yamaguchi M
AD  - Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo, Japan.
FAU - Okano, Taisuke
AU  - Okano T
AD  - Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo, Japan.
FAU - Watanabe-Kominato, Kaho
AU  - Watanabe-Kominato K
AD  - Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo, Japan.
FAU - Watanabe, Rena
AU  - Watanabe R
AD  - Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo, Japan.
FAU - Matsuyama, Taka-Aki
AU  - Matsuyama TA
AD  - Department of Pathology, National Cerebral and Cardiovascular Center, Osaka, 
      Japan.
FAU - Ishibashi-Ueda, Hatsue
AU  - Ishibashi-Ueda H
AD  - Department of Pathology, National Cerebral and Cardiovascular Center, Osaka, 
      Japan.
FAU - Koba, Shinji
AU  - Koba S
AD  - Division of Cardiology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Kobayashi, Youichi
AU  - Kobayashi Y
AD  - Division of Cardiology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Hirano, Tsutomu
AU  - Hirano T
AD  - Division of Diabetes, Metabolism, and Endocrinology, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Watanabe, Takuya
AU  - Watanabe T
AD  - Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180202
PL  - England
TA  - J Am Heart Assoc
JT  - Journal of the American Heart Association
JID - 101580524
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 670-65-5 (Neopterin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Aortic Diseases/*metabolism/pathology/prevention & control
MH  - Apoptosis/drug effects
MH  - Atherosclerosis/*metabolism/pathology/prevention & control
MH  - Cell Adhesion
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Coculture Techniques
MH  - Coronary Artery Disease/*metabolism/pathology/prevention & control
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Endothelial Cells/*metabolism/pathology
MH  - Female
MH  - Foam Cells/metabolism/pathology
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout, ApoE
MH  - Middle Aged
MH  - Muscle, Smooth, Vascular/*metabolism/pathology
MH  - Myocytes, Smooth Muscle/*metabolism/pathology
MH  - Neopterin/*metabolism
MH  - Plaque, Atherosclerotic
MH  - Signal Transduction
MH  - THP-1 Cells
MH  - Vasculitis/*metabolism/pathology/prevention & control
PMC - PMC5850243
OTO - NOTNLM
OT  - atherosclerosis
OT  - endothelial cell
OT  - inflammation
OT  - macrophage
OT  - neopterin
OT  - smooth muscle cell
EDAT- 2018/02/09 06:00
MHDA- 2019/12/18 06:00
PMCR- 2018/02/01
CRDT- 2018/02/09 06:00
PHST- 2018/02/09 06:00 [entrez]
PHST- 2018/02/09 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2018/02/01 00:00 [pmc-release]
AID - JAHA.117.007359 [pii]
AID - JAH32908 [pii]
AID - 10.1161/JAHA.117.007359 [doi]
PST - epublish
SO  - J Am Heart Assoc. 2018 Feb 2;7(3):e007359. doi: 10.1161/JAHA.117.007359.