2005 Fiscal Year Final Research Report Summary
Analysis on thrombotic tendency in obesity and diabetes by use of model mouse
| Project/Area Number |
16590934
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Nagoya University |
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Principal Investigator |
YAMAMOTO Koji Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (90362251)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUSHITA Tadashi Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (30314008)
KOJIMA Tetsuhito Nagoya University, School of Medicine, Professor, 医学部, 教授 (40161913)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Thrombosis / Obesity / Diabetes / Fibrinolysis / Stress / Atherosclerosis / Cytokine / Adipocyte |
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| Research Abstract |
Plasminogen activator inhibitor-1 (PAI-1), a principal regulator of fibrinolytic system, plays a pathological role in the development of thrombosis and cardiovascular diseases. PAI-1 is regarded to be one of adipocytokines because it is produced and secreted by adipocytes. It was experimentally revealed that PAI-1 expression in adipose tissue was dramatically increased in genetically obese mice and abundant expression of PAI-1 was localized to adipocytes in vivo. The gene expression of tissue factor (TF), an initiator of extrinsic coagulation pathway, also was significantly elevated in the epididymal and subcutaneous fat pads from obese mice. Moreover, adipocyte-derived transforming growth factor-β (TGF-β), which can induce the expression of PAI-1 and TF in adipocytes, was significantly increased in obese mice. Thus, PAI-1 and TF may be key molecules to develop thrombotic diseases in obese and diabetic patients. Meanwhile, obese patients are susceptible to thrombotic diseases associate
… More
d with stress, but the underlying mechanism is still unknown. We have begun to investigate the expression of PAI-1, in association with tissue thrombosis, using restraint-stressed obese mice. We analyzed the expression of PAI-1 after restraint (immobilization) stress in genetically obese mice in comparison with their lean counterparts. Dramatic increases in PAI-1 antigen in plasma and in tissue extracts were observed in the obese mice exposed to restraint stress. The induction of PAI-1 mRNA by stress in the tissues was also pronounced in the stressed obese mice as compared to the lean mice, especially in the hearts and adipose tissues. In situ hybridization analysis revealed that strong signals for PAI-1 mRNA were localized in the adipocytes, cardiovascular endothelial cells, and renal glomerular cells of the stressed obese mice. Histological examination revealed that renal glomerular fibrin deposition was detected only in the stressed obese mice. Thus, obesity enhances the stress-mediated PAI-1 induction in the blood and tissues. Less
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Research Products
(2 results)
