PMID- 12393670
OWN - NLM
STAT- MEDLINE
DCOM- 20030123
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 100
IP  - 12
DP  - 2002 Dec 1
TI  - Aging and obesity augment the stress-induced expression of tissue factor gene in 
      the mouse.
PG  - 4011-8
AB  - Hypercoagulability and thrombotic tendency are frequently induced by a variety of 
      stressors. Clinically, aged subjects and obese patients are more susceptible to 
      thrombotic diseases associated with stress, but the underlying mechanisms are 
      unknown. We investigated the expression of a procoagulant gene, tissue factor 
      (TF), in a mouse model of restraint stress. Twenty hours of restraint stress to 
      mice caused a substantial induction of TF mRNA in several tissues. Importantly, 
      the magnitude of induction of TF mRNA by restraint stress was larger in aged mice 
      compared with young mice. In situ hybridization analysis of the stressed aged 
      mice revealed that strong signals for TF mRNA were localized to renal epithelial 
      cells, smooth muscle cells, adventitial cells, and adipocytes but not to vascular 
      endothelial cells. These observations suggest that restraint stress induces the 
      TF expression in a tissue-specific and cell type-specific manner. Genetically 
      obese mice were also hyperresponsive to restraint stress in the induction of TF 
      gene, especially in their livers and adipose tissues. Stress-induced microthrombi 
      formation was pronounced in renal glomeruli and within the vasculature in adipose 
      tissues of aged mice. Tumor necrosis factor-alpha (TNF-alpha) antigen in plasma 
      was elevated by stress in aged mice and obese mice, and pretreatment of mice with 
      anti-TNF-alpha antibody partially attenuated the stress-mediated induction of TF 
      gene in adipose tissues in these mice. These results suggest that the induction 
      of TF gene may increase the risk of stress-associated thrombosis in older and 
      obese subjects and that TNF-alpha may be involved.
FAU - Yamamoto, Koji
AU  - Yamamoto K
AD  - First Department of Internal Medicine, Nagoya University School of Medicine, 
      Japan. kojiy@med.nagoya-u.ac.jp
FAU - Shimokawa, Takayoshi
AU  - Shimokawa T
FAU - Yi, Hong
AU  - Yi H
FAU - Isobe, Ken-Ichi
AU  - Isobe K
FAU - Kojima, Tetsuhito
AU  - Kojima T
FAU - Loskutoff, David J
AU  - Loskutoff DJ
FAU - Saito, Hidehiko
AU  - Saito H
LA  - eng
GR  - HL-47819/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020725
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9035-58-9 (Thromboplastin)
SB  - IM
MH  - *Aging/metabolism
MH  - Animals
MH  - Male
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Models, Animal
MH  - Obesity/*metabolism
MH  - RNA, Messenger/drug effects/metabolism
MH  - Stress, Physiological/*metabolism
MH  - Thromboplastin/biosynthesis/*genetics
MH  - Thrombosis/etiology
MH  - Tissue Distribution
MH  - Tumor Necrosis Factor-alpha/biosynthesis/pharmacology
MH  - *Up-Regulation
EDAT- 2002/10/24 04:00
MHDA- 2003/01/24 04:00
CRDT- 2002/10/24 04:00
PHST- 2002/10/24 04:00 [pubmed]
PHST- 2003/01/24 04:00 [medline]
PHST- 2002/10/24 04:00 [entrez]
AID - S0006-4971(20)51356-6 [pii]
AID - 10.1182/blood-2002-03-0945 [doi]
PST - ppublish
SO  - Blood. 2002 Dec 1;100(12):4011-8. doi: 10.1182/blood-2002-03-0945. Epub 2002 Jul 
      25.