Analysis of angiogenesis in fibrinolytic factordefficient mice

• Project/Area Number: 09670062
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General physiology
• Research Institution: Department of Physiology, Kinki University School of Medicine
• Principal Investigator: MATSUO Osamu Department of Physiology, Kinki University School of Medicine, Professor, 医学部, 教授 (40030879)
• Co-Investigator(Kenkyū-buntansha): OKADA Kiyotaka Department of Physiology, Kinki University School of Medicine, Assistant, 医学部, 助手 (20185432) ; FUKAO Hideharu Department of Physiology, Kinki University School of Medicine, Assistant, 医学部, 助手 (70218874) ; UESHIMA Shigeru Department of Physiology, Kinki University School of Medicine, Assistant Profess, 医学部, 助教授 (30193791)
• Project Period (FY): 1997 – 1998
• Project Status: Completed (Fiscal Year 1998)
• Budget Amount: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: Fibrinolysis / t-PA / u-PA / PAl-1 / PLGF / Capsule / Knock out mouse / Fibrin / Angiogenesis / Endothelial cells

Research Abstract

The mouse lines which lack the genes for placenta growth factor(PLGF), urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAl-1 ), respectively were established. The capsule-implantation method was useful for the analysis of wound healing process in these mice, since the formation of granulation tissues and tissue fluids were observed to be increased in a time dependent manner after the implantation of capsules. This model demonstrated that the lack of PLGF delayed the formation of granulation tissues inside the capsule at an early stage of wound healing compared with that of wild-type mouse. However, it was considerably improved in the presence of fibrin in the capsule, suggesting that fibrin acted as a good matrix for inducing tissue repair. This method was also applicable in the fibrinolytic factor-diffecient mice. The effect of fibrin in the capsule was also found to be effective for the regeneration of granulation tissues in ery fibrinolytic factor-diffecient mouse. However, there was no difference in the rate of tissue repair among these mice. Neither activities of matrix metalloproteinases in the intracapsular fluids and intracapsular tissue extracts, nor the proliferation of cultured endothelial cells were not influenced by the defficiency of these fibrinolytic factors. Therefore, the effect of u-PA, t-PA and PAl-1 on the process of angiogenesis was not evident by the capsule-implantation model.

Research Products

• [Publications] Fukao, H., Hagiya, Y., Ueshima, S., Kamiishi, H., Okada, K., and Matsuo, O.: "Fibrinolytic system in rat angiogenesis" International Journal of Angiology. (submitted).
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