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MOLECULAR AND PHYSIOLOGOCAL MECHNISM OF VASCULAR INFLAMMATION AND REMODELING AFTER VASCULAR INJURY

血管炎症和血管损伤后重塑的分子和生理机制

基本信息

批准号：
11670666
负责人：
IMAMURA Hiroshi
金额：
$ 2.43万
依托单位：
SHINSHU UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

A.Roles of P-Selectin in Inflammation, Neointimal Formation, and Vascular Remodeling after vascular injuryUsing 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 … More 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 InjuryTo 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

a . p -选择素在血管损伤后炎症、新内膜形成和血管重塑中的作用通过大鼠球囊导管损伤模型，我们研究了p -选择素在血管损伤过程中的作用。在损伤后的急性期，p -选择素在覆盖脱落节段的活化血小板和炎症小血管内皮细胞上均有强烈表达。与对照组相比，连续8天使用抗p -选择素单克隆抗体（MAb）显著抑制第14天新生内膜的形成，并且这种作用持续到第56天。在第56天，伴随血管萎缩的内皮纤维化也有所减弱。第8天，cd45阳性白细胞在新生内膜、中膜和外膜中的积累被抗p -选择素单抗显著抑制。扫描电镜显示，抗p -选择素治疗后，动脉内膜的血栓形成表面减少，在损伤后第14天呈现假内皮外观。这些结果表明，抑制p选择素介导的白细胞募集可阻止新内膜形成、外膜炎症和血管收缩的发展，并促进管腔平滑肌细胞的假内皮化。b .动脉张力和对血管活性物质的反应为了评价血管损伤后动脉壁增厚的血管张力和对血管活性物质的反应，分离正常和球囊损伤的大鼠颈动脉，测量其周壁张力的变化。高钾治疗后球囊损伤动脉基本血管张力降低。典型的血管收缩物质，去甲肾上腺素、苯肾上腺素、前列腺素（PG） f2 - α和血清素（5HT）引起的血管张力升高减弱，但与高钾诱导的血管收缩相比，球囊损伤后的相对反应没有改变。硝普钠引起的松弛作用减弱，但相对反应不变。少