PMID- 26092993
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20200930
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Linking)
VI  - 309
IP  - 5
DP  - 2015 Sep 1
TI  - 15-Lipoxygenase and 15-hydroxyeicosatetraenoic acid regulate intravascular 
      thrombosis in pulmonary hypertension.
PG  - L449-62
LID - 10.1152/ajplung.00004.2015 [doi]
AB  - Pulmonary arterial hypertension (PAH) is a disease characterized by thickening of 
      pulmonary artery walls, elevated pulmonary vascular resistance, pulmonary 
      vascular thrombotic lesions, and right heart failure. Recent studies suggest that 
      15-lipoxygenase (15-LO)/15-hydroxyeicosatetraenoic acid (15-HETE) play an 
      important role in PAH, acting on arterial walls. Here, we show evidence for the 
      action of the 15-LO/15-HETE signaling in the pulmonary vascular thrombotic 
      lesions in the experimental PAH models. Platelet deposition was augmented in rats 
      exposed to hypoxia and Sugen 5416, which were both prevented by 
      nordihydroguaiaretic acid (NDGA), a 15-LO inhibitor. Chronic hypoxic resulted in 
      the platelet deposition specifically in pulmonary vasculature, which was reversed 
      by 15-LO inhibitor. The 15-LO pathway mediated in the endothelial dysfunction 
      induced by hypoxia in vivo. Meanwhile, 15-HETE positively regulated the 
      generation of IL-6 and monocyte chemoattractant protein-1 (MCP-1). The 
      coagulation and platelet activation induced by hypoxia were reversed by 15-LO 
      inhibitor NDGA or the MCP-1 inhibitor synthesis inhibitor bindarit in rats. The 
      15-LO/15-HETE signaling promoted the coagulation and platelet activation, which 
      was suppressed by MCP-1 inhibition. These results therefore suggest that 
      15-LO/15-HETE signaling plays a role in platelet activation and pulmonary 
      vascular thrombosis in PAH, involving MCP-1.
CI  - Copyright (c) 2015 the American Physiological Society.
FAU - Shen, Tingting
AU  - Shen T
AD  - Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical 
      University (Daqing), Daqing, China;
FAU - Shi, Jiucheng
AU  - Shi J
AD  - Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical 
      University (Daqing), Daqing, China;
FAU - Wang, Na
AU  - Wang N
AD  - Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical 
      University (Daqing), Daqing, China;
FAU - Yu, Xiufeng
AU  - Yu X
AD  - Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical 
      University (Daqing), Daqing, China;
FAU - Zhang, Chen
AU  - Zhang C
AD  - Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical 
      University (Daqing), Daqing, China;
FAU - Li, Jing
AU  - Li J
AD  - Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical 
      University (Daqing), Daqing, China;
FAU - Wei, Liuping
AU  - Wei L
AD  - Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical 
      University (Daqing), Daqing, China;
FAU - Ma, Cui
AU  - Ma C
AD  - Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical 
      University (Daqing), Daqing, China;
FAU - Zhao, Xijuan
AU  - Zhao X
AD  - Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical 
      University (Daqing), Daqing, China;
FAU - Lian, Mingming
AU  - Lian M
AD  - Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical 
      University (Daqing), Daqing, China;
FAU - Jiang, Chun
AU  - Jiang C
AD  - Biology Department, Georgia State University, Atlanta, Georgia.
FAU - Zhu, Daling
AU  - Zhu D
AD  - Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical 
      University (Daqing), Daqing, China; Biopharmaceutical Key Laboratory of 
      Heilongjiang Province, Harbin Medical University, Harbin, China; and 
      dalingz@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150619
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Indazoles)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 0 (Propionates)
RN  - 0 (RNA, Small Interfering)
RN  - 73945-47-8 (15-hydroxy-5,8,11,13-eicosatetraenoic acid)
RN  - 7BO8G1BYQU (Masoprocol)
RN  - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase)
RN  - JQ11LH711M (bindarit)
SB  - IM
MH  - Animals
MH  - Arachidonate 15-Lipoxygenase/genetics/*metabolism
MH  - Blood Platelets/pathology
MH  - Cells, Cultured
MH  - Chemokine CCL2/antagonists & inhibitors
MH  - Cytokines/metabolism
MH  - Humans
MH  - Hydroxyeicosatetraenoic Acids/*metabolism
MH  - Hypertension, Pulmonary/drug therapy/*pathology
MH  - Hypoxia/blood/pathology
MH  - Indazoles/therapeutic use
MH  - Lipoxygenase Inhibitors/therapeutic use
MH  - Male
MH  - Masoprocol/therapeutic use
MH  - Platelet Activation/drug effects
MH  - Propionates/therapeutic use
MH  - Pulmonary Artery/pathology
MH  - RNA Interference
MH  - RNA, Small Interfering
MH  - Random Allocation
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects
MH  - Thrombosis/drug therapy/etiology/*metabolism
MH  - Vascular Resistance/drug effects/*physiology
OTO - NOTNLM
OT  - 15-lipoxygenase
OT  - monocyte chemoattractant protein-1
OT  - platelet
OT  - thrombosis
EDAT- 2015/06/21 06:00
MHDA- 2015/12/17 06:00
CRDT- 2015/06/21 06:00
PHST- 2015/01/07 00:00 [received]
PHST- 2015/06/12 00:00 [accepted]
PHST- 2015/06/21 06:00 [entrez]
PHST- 2015/06/21 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
AID - ajplung.00004.2015 [pii]
AID - 10.1152/ajplung.00004.2015 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2015 Sep 1;309(5):L449-62. doi: 
      10.1152/ajplung.00004.2015. Epub 2015 Jun 19.