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Redox-regulation by active oxygen species / nitric oxide in cardiovascular system

心血管系统中活性氧/一氧化氮的氧化还原调节

基本信息

批准号：
15390066
负责人：
NAKAZAWA Hiroe
金额：
$ 8.13万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390066/
关键词：
Redox Cardiovascular system Reactive oxygen species (ROS)nitric oxide PAI-1

项目摘要

Purposes1) To demonstrate active oxygen species/nitric oxide generation from endotherial and smooth muscle cells of coronary artery and cardiac myocytes as initiators of redox-regulation.2) To examine effects of lipoproteins (LDL, HDL, and TG) on PAI-1 secreation endotherial cells from the aspect of redox-regulation.3) To examine redox-regulation in the formation of unstable atheroma using mice atheroma model.Results1) The generation of active oxygen species and nitric oxide from various cells was shown to initial redox-regulation by using electron spin resonance (ESR), chemiluminescence and fluorescence methods.2) In the presence of lipoproteins endotherial cells secreated PAI-1. The amount of PAI-1 secreation was greater in HDL than in LDL additions. These results do not agree with the present knowledge of anti-atherogenic role of HDL. Thus we suggest that the increased PAI-1 in patient with atherosclerosis is not the cause but the consequence.3) Both ApoE^<-/->/iNOS^<-/-> and ApoE^<-/->/iNOS^<+/+> mice fed with atherogenic diet developed comparable size of atheroma. The important difference between the two was atheroma in ApoE^<-/->/iNOS^<+/+> mice was unstable ; less collagen and lipid-rich. Matrix metalloproteinase (MMP) was activated by possibly redox-regulated mechanism though induction of iNOS in ApoE^<-/->/iNOS^<+/+> mice.ConclusionRedox-mediated regulation appears to play an important role on cardiovascular pathogenesis.

目的1）证明冠状动脉内皮细胞、平滑肌细胞和心肌细胞产生的活性氧/一氧化氮是氧化还原调节的启动剂。（LDL，HDL，从氧化还原调节的角度探讨了三种不同的抗氧化剂对内皮细胞派-1分泌的影响。3）通过小鼠动脉粥样硬化模型研究了氧化还原调节在不稳定动脉粥样硬化形成中的作用。利用电子自旋共振（ESR）、化学发光和荧光等方法研究了不同细胞产生的活性氧和一氧化氮对氧化还原的初始调节作用。2）在脂蛋白存在下，内皮细胞分泌派-1。派-1的分泌量在HDL中比在LDL中更大。这些结果不同意目前的知识HDL的抗动脉粥样硬化的作用。3）ApoE^<-/->/iNOS^<-/->小鼠和ApoE^<-/->/iNOS^<+/+>小鼠在动脉粥样硬化形成过程中，动脉粥样硬化斑块大小相似。两者之间的重要区别是ApoE^<-/->/iNOS^<+/+>小鼠中的动脉粥样化是不稳定的;胶原蛋白较少且富含脂质。结论ApoE^<-/->/iNOS^<+/+>小鼠的基质金属蛋白酶（MMP）可能通过氧化还原调节机制被激活。