PMID- 16460448
OWN - NLM
STAT- MEDLINE
DCOM- 20060524
LR  - 20230829
IS  - 1538-7933 (Print)
IS  - 1538-7836 (Linking)
VI  - 4
IP  - 3
DP  - 2006 Mar
TI  - Thrombin and PAR-1 stimulate differentiation of bone marrow-derived endothelial 
      progenitor cells.
PG  - 656-63
AB  - Endothelial progenitor cells (EPCs) from the bone marrow play an important role 
      in vascular response to injury and ischemia. The mediators involved in the 
      mobilization, recruitment, proliferation and differentiation of EPCs are not 
      fully understood. In this study, the role of coagulation factor thrombin and 
      protease-activated receptor-1 (PAR-1) on bone marrow-derived cell proliferation 
      and differentiation was investigated. Bone marrow cells (BMCs) were isolated from 
      C57/BL6 mice and plated on fibronectin-coated flasks. Cell characteristics, 
      proliferation and the expression of endothelial cell markers were determined 
      using immunohistochemistry, thymidine uptake and fluorescence activated-cell 
      sorting (FACS), respectively. The results show that thrombin stimulated 
      enrichment of bone marrow cells with endothelial morphology, exhibiting 
      acetylated-low-density lipoprotein (LDL) uptake and isolectin staining. Thrombin 
      or PAR-1-activating peptide produced a 2- to 3-fold increase in the total number 
      of cells as well as an increase in vascular endothelial (VE)-cadherin-positive 
      cells. Thrombin treatment of VE-cadherin-negative cells prepared after cell 
      sorting resulted in the generation of 3- to 4-fold higher VE-cadherin-positive 
      cells than the untreated cultures. Increase in VE-cadherin-positive cells was 
      inhibited by hirudin and efegatran. These results provide first evidence for a 
      novel activity of thrombin and PAR-1 on bone marrow progenitor cell proliferation 
      and EPC differentiation, and suggest their potential role in vascular 
      regeneration and recanalization of thrombus.
FAU - Tarzami, S T
AU  - Tarzami ST
AD  - Lilly Research Laboratories, Indianapolis, IN 46285, USA.
FAU - Wang, G
AU  - Wang G
FAU - Li, W
AU  - Li W
FAU - Green, L
AU  - Green L
FAU - Singh, J P
AU  - Singh JP
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Antigens, CD)
RN  - 0 (Cadherins)
RN  - 0 (Hirudins)
RN  - 0 (Oligopeptides)
RN  - 0 (PAR-1-activating peptide)
RN  - 0 (Receptor, PAR-1)
RN  - 0 (cadherin 5)
RN  - EC 3.4.21.5 (Thrombin)
RN  - VT0VK2474K (efegatran)
SB  - IM
MH  - Animals
MH  - Antigens, CD
MH  - Bone Marrow Cells/cytology/drug effects/metabolism
MH  - Cadherins/metabolism
MH  - *Cell Differentiation
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/cytology/*drug effects/metabolism
MH  - Hirudins/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oligopeptides/*pharmacology
MH  - Receptor, PAR-1/*agonists
MH  - Stem Cells/cytology/*drug effects/metabolism
MH  - Thrombin/antagonists & inhibitors/*pharmacology
EDAT- 2006/02/08 09:00
MHDA- 2006/05/25 09:00
CRDT- 2006/02/08 09:00
PHST- 2006/02/08 09:00 [pubmed]
PHST- 2006/05/25 09:00 [medline]
PHST- 2006/02/08 09:00 [entrez]
AID - S1538-7836(22)12177-X [pii]
AID - 10.1111/j.1538-7836.2006.01788.x [doi]
PST - ppublish
SO  - J Thromb Haemost. 2006 Mar;4(3):656-63. doi: 10.1111/j.1538-7836.2006.01788.x.