Anticoagulant and antithrombotic activity of a new peptide pENW (pGlu-Asn-Trp).
OBJECTIVE
The aim was to test a newly discovered oligopeptide, pENW (pGlu-Asn-Trp), for its anticoagulant and antithrombotic activity in vivo, and try to investigate its underlying mechanisms.


METHODS
We measured coagulation time by the glass slide method and bleeding time by cutting of mice tails. The thrombosis models employed here included an arterio-venous shunt model and inferior vena ligation model. An ELISA (enzyme-linked immunosorbent assay) was used to analyse t-PA/PAI (tissue-type plasminogen activator/plasminogen activator inhibitor) in the blood drawn from the rats with thrombosis. The ultrastructural changes of the endothelium in the vessels developing thrombosis were observed under a transmission electron microscope.


RESULTS
We found that pENW-treated mice exhibited a prolonged coagulation time in a dose-dependent manner, but not an extended haemorrhage time. On the other hand, pENW significantly inhibited thrombus formation in both arterio-venous shunt models and inferior vena ligation models. Plasma t-PA/PAI was significantly higher as measured by ELISA. Transmission electron microscope photos of pENW-treated groups also displayed a better condition than model controls, with less erythrocytes in the vascular lumens. In addition, pENW concentration-dependently inhibited aggregation of platelets induced by ADP (adenosine 5'-diphosphate sodium salt) in rabbit platelet-rich plasma.


CONCLUSIONS
These findings support the suggestion that pENW possesses antithrombotic activity and could be a promising drug in the prevention and treatment of unwanted clot formation.
Xiong
Jing
J
Department of Physiology, School of Life Science and Technology, China Pharmaceutical University, Jiangsu, PR China.
Fang
Wei
W
Fang
Weirong
W
Bai
Li
L
Huo
Jianli
J
Kong
Yi
Y
Yunman
Li
L
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004797:Enzyme-Linked Immunosorbent Assay; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006470:Hemorrhage / Q000188:drug therapy / Q000517:prevention & control; D007275:Injections, Intravenous; D051379:Mice; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D008970:Molecular Weight; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000517:prevention & control; D014914:Whole Blood Coagulation Time
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D009842:Oligopeptides; C114010:pyroglutamyl-asparagyl-tryptophan; D000244:Adenosine Diphosphate; D011761:Pyrrolidonecarboxylic Acid