PMID- 24525312
OWN - NLM
STAT- MEDLINE
DCOM- 20150109
LR  - 20140317
IS  - 1879-2472 (Electronic)
IS  - 0049-3848 (Linking)
VI  - 133
IP  - 4
DP  - 2014 Apr
TI  - MC-002 exhibits positive effects against platelets aggregation and endothelial 
      dysfunction through thromboxane A2 inhibition.
PG  - 610-5
LID - S0049-3848(14)00053-X [pii]
LID - 10.1016/j.thromres.2014.01.029 [doi]
AB  - INTRODUCTION: Thromboxane A2 (TXA2) induces platelet aggregation and 
      vasoconstriction, and agents that inhibit TXA2 production or interaction with 
      receptors may exert potential application in stroke therapy. AIM: To illustrate 
      the platelet aggregation antagonistic and endothelial protective effect of (E) - 
      3 - (3 - methoxy - 4 - ((3, 5, 6 - trimethylpyrazin - 2 - yl) methoxy) phenyl) 
      sodium acrylate (MC-002) through TXA2 inhibition and underline mechanisms. 
      MATERIALS AND METHODS: Platelets aggregation and thoracic aorta ring contraction 
      of rabbits were induced by U46619. Human umbilical vein endothelial cells 
      (HUVECs) were further applied to explore the protective effect of MC-002 on 
      endothelium when exposed to tumor necrosis factor - alpha (TNF-alpha). MTT method was 
      used to assess cell damage, and ELISA analysis was exerted to estimate nitrogen 
      monoxide (NO), endothelin-1 (ET-1), thromboxane B2 (TXB2) and 
      6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) releasing. Fluorescence spectrophotometry 
      was conducted to determine intracellular calcium concentration ([Ca(2+)]i), and 
      western blotting method was applied to evaluate the protein expressions of 
      intracellular adhesion molecule-1 (ICAM-1), P-selectin and nuclear factor-kappa B 
      (NF-kappaB). RESULTS AND CONCLUSIONS: TXA2 analog U46619 mediated obvious platelet 
      aggregation and vasoconstriction. MC-002 inhibited platelet aggregation through 
      administration in vivo and incubation with platelet in vitro, and relaxed aorta 
      ring in endothelium dependent manner. MC-002 alleviated cell damage, [Ca(2+)]i 
      overload, ET-1 overexcretion and TXB2 activation, but improved NO availability 
      reduction in HUVECs treated with TNF-alpha. Furthermore, MC-002 downregulated ICAM-1, 
      P-selectin and NF-kappaB overexpression induced by TNF-alpha. In conclusion, MC-002 
      exerted antiplatelet aggregation effect through TXA2 inhibition and relieved 
      inflammatory injury of endothelial cells through NF-kappaB signal pathway.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Fang, Weirong
AU  - Fang W
AD  - State Key Laboratory of Natural Medicines, Department of Physiology, China 
      Pharmaceutical University, Nanjing 210009, P. R. China.
FAU - Wei, Jie
AU  - Wei J
AD  - State Key Laboratory of Natural Medicines, Department of Physiology, China 
      Pharmaceutical University, Nanjing 210009, P. R. China.
FAU - Han, Dan
AU  - Han D
AD  - State Key Laboratory of Natural Medicines, Department of Physiology, China 
      Pharmaceutical University, Nanjing 210009, P. R. China.
FAU - Chen, Xi
AU  - Chen X
AD  - State Key Laboratory of Natural Medicines, Department of Physiology, China 
      Pharmaceutical University, Nanjing 210009, P. R. China.
FAU - He, Guangwei
AU  - He G
AD  - Hefei Yigong Medicine Co., Ltd., Hefei 230088, P. R. China.
FAU - Wu, Qiang
AU  - Wu Q
AD  - Hefei Yigong Medicine Co., Ltd., Hefei 230088, P. R. China.
FAU - Chu, Shaoxing
AU  - Chu S
AD  - Hefei Yigong Medicine Co., Ltd., Hefei 230088, P. R. China.
FAU - Li, Yunman
AU  - Li Y
AD  - State Key Laboratory of Natural Medicines, Department of Physiology, China 
      Pharmaceutical University, Nanjing 210009, P. R. China. Electronic address: 
      yunmanlicpu@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140129
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Acrylates)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Prostaglandin Antagonists)
RN  - 0 (Pyrans)
RN  - 0 (Receptors, Thromboxane A2, Prostaglandin H2)
RN  - 57576-52-0 (Thromboxane A2)
SB  - IM
MH  - Acrylates/pharmacology
MH  - Animals
MH  - Humans
MH  - Male
MH  - Platelet Aggregation/drug effects
MH  - Platelet Aggregation Inhibitors/pharmacology
MH  - Prostaglandin Antagonists/*pharmacology
MH  - Pyrans/*pharmacology
MH  - Rabbits
MH  - Random Allocation
MH  - Receptors, Thromboxane A2, Prostaglandin H2/antagonists & inhibitors/metabolism
MH  - Thromboxane A2/*antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - Inflammation
OT  - MC-002
OT  - Platelet aggregation
OT  - TXA(2)
EDAT- 2014/02/15 06:00
MHDA- 2015/01/13 06:00
CRDT- 2014/02/15 06:00
PHST- 2013/11/07 00:00 [received]
PHST- 2014/01/10 00:00 [revised]
PHST- 2014/01/26 00:00 [accepted]
PHST- 2014/02/15 06:00 [entrez]
PHST- 2014/02/15 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
AID - S0049-3848(14)00053-X [pii]
AID - 10.1016/j.thromres.2014.01.029 [doi]
PST - ppublish
SO  - Thromb Res. 2014 Apr;133(4):610-5. doi: 10.1016/j.thromres.2014.01.029. Epub 2014 
      Jan 29.