PMID- 24832568
OWN - NLM
STAT- MEDLINE
DCOM- 20160215
LR  - 20150515
IS  - 1369-1635 (Electronic)
IS  - 0953-7104 (Linking)
VI  - 26
IP  - 4
DP  - 2015
TI  - Antiplatelet aggregation and endothelial protection of I4, a new synthetic 
      anti-diabetes sulfonylurea compound.
PG  - 342-8
LID - 10.3109/09537104.2014.912749 [doi]
AB  - I4 is a new synthetic anti-diabetes sulfonylurea compound. The aim of present 
      study was to investigate the preventive effects and primary action mechanisms of 
      I4 on platelet-mediated arterial thrombosis. Platelet aggregation and 
      5-hydroxytryptamine (5-HT) secretion ex vivo was detected. The time-to-occlusion 
      (TTO), thrombus weight and content of von Willebrand factor (vWF) in rat model of 
      electrical- and ferric chloride-induced vessel occlusion were determined. 
      Meanwhile, a rat model of type 2 diabetes mellitus (T2DM) was established to 
      evaluate the effect of I4 on levels of plasma p-selectin, 6-keto-prostaglandin 
      F1a (6-keto-PGF1a), thromboxane B2 (TXB2), tissue-type plasminogen activator 
      (t-PA) and type-1 plasminogen activator inhibitor (PAI-1). NO synthesis, NOS 
      activity, adhesion of platelet toward endothelial cell and intercellular adhesion 
      molecule-1 (ICAM-1) expression were examined. Results showed that I4 exhibited a 
      higher inhibitory potency than Glimepiride on ADP-induced platelet aggregation 
      and 5-HT release ex vivo. In addition, I4 reduced the thrombus weight and content 
      of vWF and markedly prolonged TTO. Oral administration of I4 (1  approximately  10 mg/kg) 
      inhibited p-selectin production, elevated the ratio of plasma 6-keto-PGF1a/TXB2 
      and t-PA/PAI-1 in T2DM rats. Furthermore, I4 significantly improved NO synthesis 
      and NOS activity, lowered adhesion ratio of platelet toward endothelial cells and 
      ICAM-1 expression on HUVECs. These observations suggest that I4 markedly improves 
      platelet-mediated arterial thrombosis by inhibiting platelet activation and 
      release reaction, ameliorating the endothelial dysfunction such as the 
      suppression of vWF production and the reduction of the overexpression of ICAM-1, 
      displayed its potential in alleviating diabetes-associated vascular 
      complications.
FAU - Ma, Lingman
AU  - Ma L
AD  - Department of Pharmacology, China Pharmaceutical University , Nanjing , P.R. 
      China.
FAU - Lu, Na
AU  - Lu N
FAU - Wu, Guanzhong
AU  - Wu G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140515
PL  - England
TA  - Platelets
JT  - Platelets
JID - 9208117
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Sulfonylurea Compounds)
SB  - IM
MH  - Animals
MH  - Blood Platelets/*drug effects/immunology
MH  - Diabetes Mellitus, Type 2/*blood/drug therapy
MH  - Humans
MH  - Male
MH  - Platelet Activation/drug effects
MH  - Platelet Aggregation/*drug effects
MH  - Platelet Aggregation Inhibitors/*pharmacology
MH  - Platelet Function Tests
MH  - Rabbits
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sulfonylurea Compounds/*pharmacology
OTO - NOTNLM
OT  - Endothelial dysfunction I4
OT  - platelet hyperreactivity
OT  - platelet-mediated thrombosis
EDAT- 2014/05/17 06:00
MHDA- 2016/02/16 06:00
CRDT- 2014/05/17 06:00
PHST- 2014/05/17 06:00 [entrez]
PHST- 2014/05/17 06:00 [pubmed]
PHST- 2016/02/16 06:00 [medline]
AID - 10.3109/09537104.2014.912749 [doi]
PST - ppublish
SO  - Platelets. 2015;26(4):342-8. doi: 10.3109/09537104.2014.912749. Epub 2014 May 15.