2000 Fiscal Year Final Research Report Summary
MOLECULAR AND PHYSIOLOGOCAL MECHNISM OF VASCULAR INFLAMMATION AND REMODELING AFTER VASCULAR INJURY
| Project/Area Number |
11670666
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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 |
Circulatory organs internal medicine
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| Research Institution | SHINSHU UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
IMAMURA Hiroshi SHINSHU UNIVERSITY SCHOOL OF MEDICINE, LECTURER, 医学部, 講師 (60283264)
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| Co-Investigator(Kenkyū-buntansha) |
ISOBE Mitsuaki TOKYO MEDICAL AND DENTAL UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (80176263)
WATANBE Noboru SHINSHU UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部・附属病院, 助手 (50303467)
UCHIKAWA Shin-ichiro SHINSHU UNIVERSITY SCHOOL OF MEDICINE, ASSISTATNT PROFESSOR, 医学部・附属病院, 助手 (50324265)
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| Project Period (FY) |
1999 – 2000
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| Keywords | P-selectin / leukocyte / platelet / restenosis / remodeling / vascular tone / 血管反応性 / 血管平滑筋 |
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| Research Abstract |
A.Roles of P-Selectin in Inflammation, Neointimal Formation, and Vascular Remodeling after vascular injury
Using a rat balloon catheter-induced injury model, we examined the role of P-selectin in vascular injury processes. In the acute phase after the injury, P-selectin was intensely expressed on both activated platelets covering the denuded segment and endothelial cells of the inflamed adventitial small vessels. Treatment with an anti-P-selectin monoclonal antibody (MAb) for 8 consecutive days significantly inhibited neointimal formation at day 14, and this effect persisted at day 56, as compared with the control group. Vascular shrinking accompanying adventitial fibrosis was also attenuated at day 56. Accumulation of CD45-positive leukocytes in the developing neointima, media and adventitia at day 8 was significantly inhibited by treatment with the anti-P-selectin MAb. Scanning electron microscopy demonstrated that anti-P-selectin treatment resulted in a less thrombogenic surface of t
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he arterial intima, which featured a pseudoendothelial appearance at day 14 after injury. These results suggest that inhibition of P-selectin-mediated leukocyte recruitment prevents the development of neointimal formation, adventitial inflammation, and vascular shrinking and promotes pseudoendothelialization by luminal smooth muscle cells. This treatment thus beneficially affects vascular remodeling after balloon injury in rat.
B.Arterial Tone and Responses to Vasoactive Substances After Balloon Injury
To evaluate vascular tone and response to vasoactive substances of thickening arterial wall after vascular injury, normal and balloon injured rat carotid arteries were isolated and change in circumferential wall tension was measured. Basic vascular tone of balloon injured artery after high potassium treatment was diminished. Typical vaso-constrictive substances, norepinephrine, phenylephrine, prostaglandin (PG) F2-alpha, and Serotonin (5HT) induced increases in vascular tension were attenuated, but relative responses compared with high potassium induced contraction were not changed after balloon injury. Relaxation induced by sodium nitroprusside was diminished, but relative responses were not changed. Less
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