PMID- 9157603
OWN - NLM
STAT- MEDLINE
DCOM- 19970520
LR  - 20031114
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 77
IP  - 2
DP  - 1997 Feb
TI  - Antithrombin III-independent effect of depolymerized holothurian 
      glycosaminoglycan (DHG) on acute thromboembolism in mice.
PG  - 399-402
AB  - A previous study in this laboratory showed that depolymerized holothurian 
      glycosaminoglycan (DHG) has two different antithrombin III (ATIII)-independent 
      inhibitory effects on the in vitro blood coagulation system: heparin cofactor II 
      (HCII)-dependent inhibition of thrombin, and ATIII- and HCII-independent 
      inhibition of factor X activation by factor IXa-factor VIIIa complex (Nagase et 
      al. Blood 85, 1527-1534, 1995). In the present study, we compared the 
      antithrombotic effects of DHG in normal and in ATIII-deficient mice with those of 
      unfractionated heparin (UFH) and low molecular weight heparin (LMWH). DHG, unlike 
      UFH and LMWH, exerted an in vivo antithrombotic effect even in mice with 
      decreased plasma ATIII activity (about 30% of normal). We then compared the 
      anticoagulant and antithrombotic effects of DHG in mice with those of high 
      molecular weight (HMW)-DHG, low molecular weight (LMW)-DHG, and dermatan sulfate 
      (DS). In terms of in vitro anticoagulant activity assessed by use of purified 
      human components, DHGs (DHG, HMW-DHG, and LMW-DHG) had different anti-thrombin 
      activity in the presence of HCII and anti-factor Xase activities, which 
      differences were dependent on the molecular weight. With respect to in vivo 
      antithrombotic activity, DHG, HMW-DHG, and LMW-DHG showed almost the same 
      inhibitory effect on acute thromboembolism in mice (minimum effective dose [MED]: 
      > 0.3 mg/kg). Since the antithrombotic activities of DHGs were not correlated 
      with the anticoagulant-specific activities, the contribution of the two 
      anticoagulant activities to the in vivo antithrombotic effect of DHGs remains 
      unknown. However, DHG was more effective against acute thromboembolism in mice 
      than DS (MED > 1 or > 3 mg/kg), which showed no inhibitory activity toward factor 
      Xase. Therefore, it seems that factor Xase inhibition contributes greatly to the 
      antithrombotic effect of DHG and that DHG exerts this effect in mice mainly by 
      inhibiting factor Xase.
FAU - Nagase, H
AU  - Nagase H
AD  - Taiho Pharmaceutical Co., Ltd, Tokushima, Japan.
FAU - Kitazato, K T
AU  - Kitazato KT
FAU - Sasaki, E
AU  - Sasaki E
FAU - Hattori, M
AU  - Hattori M
FAU - Kitazato, K
AU  - Kitazato K
FAU - Saito, H
AU  - Saito H
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Glycosaminoglycans)
RN  - 9000-94-6 (Antithrombin III)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Animals
MH  - Antithrombin III/*physiology
MH  - Antithrombin III Deficiency
MH  - Cattle
MH  - Fibrinolytic Agents/chemistry/isolation & purification/*therapeutic use
MH  - Glycosaminoglycans/chemistry/isolation & purification/*therapeutic use
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Sea Cucumbers/*chemistry
MH  - Thrombin/toxicity
MH  - Thromboembolism/chemically induced/*drug therapy
MH  - *Thrombolytic Therapy
EDAT- 1997/02/01 00:00
MHDA- 1997/02/01 00:01
CRDT- 1997/02/01 00:00
PHST- 1997/02/01 00:00 [pubmed]
PHST- 1997/02/01 00:01 [medline]
PHST- 1997/02/01 00:00 [entrez]
PST - ppublish
SO  - Thromb Haemost. 1997 Feb;77(2):399-402.