PMID- 20088932
OWN - NLM
STAT- MEDLINE
DCOM- 20100708
LR  - 20230829
IS  - 1538-7836 (Electronic)
IS  - 1538-7836 (Linking)
VI  - 8
IP  - 4
DP  - 2010 Apr
TI  - Pulmonary hypertension is ameliorated in mice deficient in thrombin-activatable 
      fibrinolysis inhibitor.
PG  - 808-16
LID - 10.1111/j.1538-7836.2010.03751.x [doi]
AB  - BACKGROUND: The fibrinolytic system has been implicated in the pathogenesis of 
      pulmonary hypertension (PH). Thrombin-activatable fibrinolysis inhibitor (TAFI) 
      inhibits fibrinolysis and therefore its absence would be expected to increase 
      fibrinolysis and ameliorate PH. OBJECTIVE: The objective of the present study was 
      to evaluate the effect of TAFI deficiency on pulmonary hypertension in the mouse. 
      METHODS AND RESULTS: PH was induced in C57/Bl6 wild-type (WT) or TAFI-deficient 
      (KO) mice by weekly subcutaneous treatment with 600 mg kg(-1) monocrotaline (MCT) 
      for 8 weeks. PH was inferred from right heart hypertrophy measured using the 
      ratio of right ventricle-to-left ventricle-plus-septum weight [RV/(LV+S)]. 
      Pulmonary vascular remodeling was analyzed by morphometry. TAFI-deficient 
      MCT-treated and wild-type MCT-treated mice suffered similar weight loss. 
      TAFI-deficient MCT-treated mice had reduced levels of total protein and tumor 
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), transforming growth 
      factor-beta (TGF-beta) and monocyte chemoattractant protein-1 (MCP-1) in 
      bronchial alveolar lavage compared with wild-type MCT-treated mice. The ratio of 
      RV to (LV+S) weight was significantly higher in WT/MCT than in KO/MCT mice. The 
      pulmonary artery wall area and vascular stenosis were both greater in MCT-treated 
      WT mice compared with MCT-treated TAFI-deficient mice. CONCLUSIONS: 
      TAFI-deficient MCT-treated mice had less pulmonary hypertension, vascular 
      remodeling and reduced levels of cytokines compared with MCT-treated WT animals, 
      possibly as a result of reduced coagulation activation.
FAU - Qin, L
AU  - Qin L
AD  - Department of Immunology, Mie University School of Medicine, Edobashi 2-174, Tsu 
      city, Mie 514-8507, Japan.
FAU - D'Alessandro-Gabazza, C N
AU  - D'Alessandro-Gabazza CN
FAU - Aoki, S
AU  - Aoki S
FAU - Gil-Bernabe, P
AU  - Gil-Bernabe P
FAU - Yano, Y
AU  - Yano Y
FAU - Takagi, T
AU  - Takagi T
FAU - Boveda-Ruiz, D
AU  - Boveda-Ruiz D
FAU - Ramirez Marmol, A Y
AU  - Ramirez Marmol AY
FAU - San Martin Montenegro, V T
AU  - San Martin Montenegro VT
FAU - Toda, M
AU  - Toda M
FAU - Miyake, Y
AU  - Miyake Y
FAU - Taguchi, O
AU  - Taguchi O
FAU - Takei, Y
AU  - Takei Y
FAU - Morser, J
AU  - Morser J
FAU - Gabazza, E C
AU  - Gabazza EC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100117
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Biomarkers)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 73077K8HYV (Monocrotaline)
RN  - EC 3.4.17.20 (Carboxypeptidase B2)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Bronchoalveolar Lavage Fluid/immunology
MH  - Capillary Permeability
MH  - Carboxypeptidase B2/*deficiency/genetics
MH  - Chemokine CCL2/metabolism
MH  - Disease Models, Animal
MH  - *Fibrinolysis/genetics
MH  - Hypertension, Pulmonary/blood/chemically 
      induced/genetics/immunology/pathology/*prevention & control
MH  - Hypertrophy, Right Ventricular/blood/prevention & control
MH  - Inflammation Mediators/metabolism
MH  - Interleukin-6/metabolism
MH  - Lung/blood supply/immunology/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Monocrotaline
MH  - Platelet-Derived Growth Factor/metabolism
MH  - Pulmonary Artery/metabolism/pathology
MH  - Transforming Growth Factor beta1/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Weight Loss
EDAT- 2010/01/22 06:00
MHDA- 2010/07/09 06:00
CRDT- 2010/01/22 06:00
PHST- 2010/01/22 06:00 [entrez]
PHST- 2010/01/22 06:00 [pubmed]
PHST- 2010/07/09 06:00 [medline]
AID - S1538-7836(22)11320-6 [pii]
AID - 10.1111/j.1538-7836.2010.03751.x [doi]
PST - ppublish
SO  - J Thromb Haemost. 2010 Apr;8(4):808-16. doi: 10.1111/j.1538-7836.2010.03751.x. 
      Epub 2010 Jan 17.