PMID- 10928483
OWN - NLM
STAT- MEDLINE
DCOM- 20010202
LR  - 20180815
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 84
IP  - 1
DP  - 2000 Jul
TI  - Inhibition of tissue factor synthesis by disruption of ERK kinases and PKC 
      signaling pathways in human vascular SMCs.
PG  - 129-36
AB  - Tissue Factor (TF), the receptor for plasma VII/VIIa and the initiator of blood 
      coagulation, is inducible in vascular smooth muscle cells (SMCs) by growth 
      factors and bacterial lysopolysaccharides (LPS) and is expressed in vivo after 
      vascular injury. As TF expression is a determinant of the thrombogenicity of 
      vascular lesions, we investigated the signal pathways involved in this process. 
      Human vascular SMCs were obtained from normal arteries and made quiescent by 
      serum deprivation. Baseline TF antigen and activity were up-regulated by various 
      agonists: fetal calf serum (FCS), LPS, and platelet derived growth factor (PDGF) 
      being the most effective but with different kinetics. TF expression induced by 
      LPS was transient with a maximum 6 h after stimulation and returned to baseline 
      levels after 24 h whereas TF expression induced by serum or PDGF was sustained 
      for at least 24 h. Rapid and transient activation of Extracellular 
      signal-Regulated Kinase (ERK) was observed after stimulation by PDGF and FCS, but 
      not by LPS. The role of ERK, Ras and protein kinase C activities were 
      investigated using specific inhibitors, PD 98059, manumycin A and calphostin C 
      respectively. For TF induction by LPS, PKC activity was required and the ERK/Ras 
      pathway was not involved. In contrast, the effect of PDGF was strictly ERK and 
      Ras dependent, but partially prevented by PKC inhibitors. TF induction by FCS was 
      ERK dependent but partially Ras and PKC dependent. In conclusion, TF expression 
      appears to be a non-specific response of SMCs to numerous stimuli through 
      multiple signal pathways which differ according to the inducing agent.
FAU - Xuereb, J M
AU  - Xuereb JM
AD  - Laboratoire de Recerche sur l'Hemostase, Hopital Purpan, Toulouse, France.
FAU - Sie, P
AU  - Sie P
FAU - Boneu, B
AU  - Boneu B
FAU - Constans, J
AU  - Constans J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Culture Media)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Naphthalenes)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Polyenes)
RN  - 0 (Polyunsaturated Alkamides)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 9035-58-9 (Thromboplastin)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.21.5 (Thrombin)
RN  - I271P23G24 (calphostin C)
RN  - OIQ298X4XD (manumycin)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Cattle/blood
MH  - Cells, Cultured/drug effects/metabolism
MH  - Culture Media/pharmacology
MH  - Culture Media, Serum-Free
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/*pharmacology
MH  - Fetal Blood/physiology
MH  - Fibroblast Growth Factor 2/pharmacology
MH  - Flavonoids/pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - Genes, Immediate-Early
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - MAP Kinase Signaling System/*drug effects/physiology
MH  - Mammary Arteries/cytology
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*physiology
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*physiology
MH  - Muscle, Smooth, Vascular/*drug effects/metabolism
MH  - Naphthalenes/pharmacology
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - Polyenes/pharmacology
MH  - Polyunsaturated Alkamides
MH  - Protein Kinase C/antagonists & inhibitors/*physiology
MH  - Thrombin/pharmacology
MH  - Thromboplastin/*biosynthesis
EDAT- 2000/08/06 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/08/06 11:00
PHST- 2000/08/06 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/08/06 11:00 [entrez]
AID - 00070129 [pii]
PST - ppublish
SO  - Thromb Haemost. 2000 Jul;84(1):129-36.