PMID- 19608750
OWN - NLM
STAT- MEDLINE
DCOM- 20091027
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 114
IP  - 15
DP  - 2009 Oct 8
TI  - Tissue-type plasminogen activator (t-PA) induces stromelysin-1 (MMP-3) in 
      endothelial cells through activation of lipoprotein receptor-related protein.
PG  - 3352-8
LID - 10.1182/blood-2009-02-203919 [doi]
AB  - Tissue-type plasminogen activator (t-PA) is approved for treatment of ischemic 
      stroke patients, but it increases the risk of intracranial bleeding (ICB). 
      Previously, we have shown in a mouse stroke model that stromelysin-1 (matrix 
      metalloproteinase-3 [MMP-3]) induced in endothelial cells was critical for ICB 
      induced by t-PA. In the present study, using bEnd.3 cells, a mouse brain-derived 
      endothelial cell line, we showed that MMP-3 was induced by both ischemic stress 
      and t-PA treatment. This induction by t-PA was prevented by inhibition either of 
      low-density lipoprotein receptor-related protein (LRP) or of nuclear 
      factor-kappaB activation. LRP was up-regulated by ischemic stress, both in bEnd.3 
      cells in vitro and in endothelial cells at the ischemic damage area in the mouse 
      stroke model. Furthermore, inhibition of LRP suppressed both MMP-3 induction in 
      endothelial cells and the increase in ICB by t-PA treatment after stroke. These 
      findings indicate that t-PA deteriorates ICB via MMP-3 induction in endothelial 
      cells, which is regulated through the LRP/nuclear factor-kappaB pathway.
FAU - Suzuki, Yasuhiro
AU  - Suzuki Y
AD  - Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, 
      Japan, Japan.
FAU - Nagai, Nobuo
AU  - Nagai N
FAU - Yamakawa, Kasumi
AU  - Yamakawa K
FAU - Kawakami, Junichi
AU  - Kawakami J
FAU - Lijnen, H Roger
AU  - Lijnen HR
FAU - Umemura, Kazuo
AU  - Umemura K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090716
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (LDL-Receptor Related Proteins)
RN  - 0 (NF-kappa B)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.17 (Mmp3 protein, mouse)
SB  - IM
CIN - Blood. 2009 Oct 8;114(15):3136-7. PMID: 19815679
MH  - Animals
MH  - Brain Ischemia/*enzymology/genetics
MH  - Cell Line, Transformed
MH  - Disease Models, Animal
MH  - Endothelial Cells/*enzymology
MH  - Enzyme Induction/drug effects
MH  - Humans
MH  - LDL-Receptor Related Proteins/genetics/*metabolism
MH  - Male
MH  - Matrix Metalloproteinase 3/*biosynthesis/genetics
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Stroke/*enzymology/genetics
MH  - Tissue Plasminogen Activator/*pharmacology
EDAT- 2009/07/18 09:00
MHDA- 2009/10/29 06:00
CRDT- 2009/07/18 09:00
PHST- 2009/07/18 09:00 [entrez]
PHST- 2009/07/18 09:00 [pubmed]
PHST- 2009/10/29 06:00 [medline]
AID - S0006-4971(20)36813-0 [pii]
AID - 10.1182/blood-2009-02-203919 [doi]
PST - ppublish
SO  - Blood. 2009 Oct 8;114(15):3352-8. doi: 10.1182/blood-2009-02-203919. Epub 2009 
      Jul 16.