PMID- 10362798
OWN - NLM
STAT- MEDLINE
DCOM- 19990714
LR  - 20191210
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 154
IP  - 6
DP  - 1999 Jun
TI  - Role and localization of urokinase receptor in the formation of new microvascular 
      structures in fibrin matrices.
PG  - 1731-42
AB  - Fibrin or a fibrinous exudate can facilitate angiogenesis in many pathological 
      conditions. In vitro, the outgrowth of capillary-like structures in fibrin can be 
      mimicked by exposing human microvascular endothelial cells (hMVECs) to an 
      angiogenic growth factor and tumor necrosis factor (TNF)-alpha. Urokinase-type 
      plasminogen activator (u-PA) and plasmin activities are required for this 
      angiogenic process. This study focuses on the role and localization of the u-PA 
      receptor (u-PAR) in newly formed microvascular structures. The u-PAR-blocking 
      monoclonal antibody (MAb) H-2 completely inhibited the formation of 
      capillary-like tubular structures induced by exposure of hMVECs to basic 
      fibroblast growth factor and TNF-alpha. This was accompanied by a several-fold 
      increase in u-PA accumulation in the conditioned medium. The effect of MAb H-2 
      was not caused by blocking cellular activation by u-PA/u-PAR interaction, as the 
      amino-terminal fragment (ATF) of u-PA, which also activates u-PAR, prevented tube 
      formation. In addition, the inhibition by MAb H-2 was not due to an effect of the 
      antibody on u-PAR-vitronectin binding. These data show that inhibition of tube 
      formation can be caused not only by inhibition of u-PA or plasmin activities but 
      also by unavailability of the u-PAR for cell-bound proteolysis. 
      Immunohistochemical analysis showed that in in vitro angiogenesis u-PAR and u-PA 
      were localized on the invading, tube-forming hMVECs and not on the endothelial 
      cells that are located on top of the fibrin matrix. u-PAR and u-PA were also 
      prominently expressed on endothelial cells of neovessels present in an 
      atherosclerotic plaque. These data may give more insight into the role of u-PAR 
      in repair-associated angiogenesis.
FAU - Kroon, M E
AU  - Kroon ME
AD  - Gaubius Laboratory, Leiden University Hospital, Groningen Leiden The Netherlands.
FAU - Koolwijk, P
AU  - Koolwijk P
FAU - van Goor, H
AU  - van Goor H
FAU - Weidle, U H
AU  - Weidle UH
FAU - Collen, A
AU  - Collen A
FAU - van der Pluijm, G
AU  - van der Pluijm G
FAU - van Hinsbergh, V W
AU  - van Hinsbergh VW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytokines)
RN  - 0 (PLAUR protein, human)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Vitronectin)
RN  - 9001-31-4 (Fibrin)
RN  - EC 2.5.1.18 (GST-RAP protein, recombinant)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 3.4.21.- (Plasminogen Activators)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Antibodies, Monoclonal/metabolism/pharmacology
MH  - Arteriosclerosis/metabolism
MH  - Carrier Proteins/pharmacology
MH  - Cells, Cultured
MH  - Cytokines/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/cytology/drug effects/metabolism
MH  - Fibrin/physiology
MH  - Glutathione Transferase/pharmacology
MH  - Humans
MH  - Immunohistochemistry
MH  - Neovascularization, Physiologic/drug effects/*physiology
MH  - Plasminogen Activators/immunology/*metabolism/*physiology
MH  - Receptors, Cell Surface/immunology/*metabolism/*physiology
MH  - Receptors, Urokinase Plasminogen Activator
MH  - Recombinant Fusion Proteins/pharmacology
MH  - Urokinase-Type Plasminogen Activator/antagonists & 
      inhibitors/metabolism/pharmacokinetics
MH  - Vitronectin/metabolism
PMC - PMC1866643
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
PMCR- 1999/12/01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
PHST- 1999/12/01 00:00 [pmc-release]
AID - S0002-9440(10)65429-6 [pii]
AID - 1743 [pii]
AID - 10.1016/S0002-9440(10)65429-6 [doi]
PST - ppublish
SO  - Am J Pathol. 1999 Jun;154(6):1731-42. doi: 10.1016/S0002-9440(10)65429-6.