PMID- 19535796
OWN - NLM
STAT- MEDLINE
DCOM- 20090930
LR  - 20211020
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 114
IP  - 8
DP  - 2009 Aug 20
TI  - Role of tissue factor in a mouse model of thrombotic microangiopathy induced by 
      antiphospholipid antibodies.
PG  - 1675-83
LID - 10.1182/blood-2009-01-199117 [doi]
AB  - Using different mouse monoclonal and human antiphospholipid (aPL) antibodies, we 
      developed a new animal model of renal injury that shares many features with 
      thrombotic microangiopathy (TMA). We found that more than 1 mechanism/signaling 
      pathway is involved in glomerular injury induced by aPL antibodies in this model. 
      Both complement-dependent and complement-independent pathways were identified 
      that lead to glomerular endothelial cell damage and renal function impairment. We 
      also found that C5a-C5aR interaction is a crucial step for the activation of the 
      coagulation cascade and glomerular injury induced by complement-activating 
      antibodies. In addition, our studies demonstrated complement-independent 
      mechanisms in which reactivity with beta(2) glycoprotein I (beta2GPI) plays an 
      important role in aPL-induced glomerular damage and renal failure. Independently 
      of the mechanism responsible for aPL-induced TMA, mice that express low levels of 
      tissue factor (TF) were protected from glomerular injury. That genetic reduction 
      of TF prevents renal injury induced by different aPL antibodies indicates that TF 
      is a common mediator of glomerular damage and a possible target for selective 
      pharmacologic intervention. Treatment with pravastatin, which down-regulates 
      glomerular TF synthesis, prevents aPL-induced TMA in this mouse model, thus 
      emphasizing that targeting TF might be a good therapeutic intervention in 
      patients with TMA.
FAU - Seshan, Surya V
AU  - Seshan SV
AD  - Department of Pathology, Department of Medicine, Weill Cornell Medical College, 
      New York, NY, USA.
FAU - Franzke, Claus-Werner
AU  - Franzke CW
FAU - Redecha, Patricia
AU  - Redecha P
FAU - Monestier, Marc
AU  - Monestier M
FAU - Mackman, Nigel
AU  - Mackman N
FAU - Girardi, Guillermina
AU  - Girardi G
LA  - eng
GR  - R01 HL048872/HL/NHLBI NIH HHS/United States
GR  - R01 HL048872-04/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090617
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Antiphospholipid)
RN  - 0 (Antibodies, Monoclonal)
RN  - 9035-58-9 (Thromboplastin)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Antibodies, Antiphospholipid/*adverse effects
MH  - Antibodies, Monoclonal/immunology/metabolism
MH  - Antigen-Antibody Reactions/immunology
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Kidney Glomerulus/immunology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microvessels/pathology
MH  - Middle Aged
MH  - Renal Insufficiency/etiology/genetics/immunology/metabolism
MH  - Thromboplastin/genetics/metabolism/*physiology
MH  - Thrombosis/*etiology/genetics/metabolism/pathology
PMC - PMC2927091
EDAT- 2009/06/19 09:00
MHDA- 2009/10/01 06:00
PMCR- 2009/08/20
CRDT- 2009/06/19 09:00
PHST- 2009/06/19 09:00 [entrez]
PHST- 2009/06/19 09:00 [pubmed]
PHST- 2009/10/01 06:00 [medline]
PHST- 2009/08/20 00:00 [pmc-release]
AID - S0006-4971(20)37194-9 [pii]
AID - 2009/199117 [pii]
AID - 10.1182/blood-2009-01-199117 [doi]
PST - ppublish
SO  - Blood. 2009 Aug 20;114(8):1675-83. doi: 10.1182/blood-2009-01-199117. Epub 2009 
      Jun 17.