期刊论文详细信息
Significance of chymase-dependent angiotensin II-forming pathway in the development of vascular proliferation
Article
关键词: ENDOTHELIAL GROWTH-FACTOR;    COLLAGEN MESSENGER-RNA;    VEIN BYPASS GRAFTS;    RAT INJURED ARTERY;    MAST-CELL GRANULE;    CONVERTING ENZYME;    ATHEROSCLEROTIC AORTA;    INTIMAL HYPERPLASIA;    UP-REGULATION;    EXPRESSION;   
DOI  :  10.1161/hc3601.094304
来源: SCIE
【 摘 要 】

Background-Vascular tissues of humans and dogs contain chymase as an angiotensin II-forming enzyme. In this study, we investigated whether chymase-dependent angiotensin II formation plays a crucial role in the development of vascular proliferation in dog grafted veins. Methods and Results-The right external jugular vein of dogs was grafted to the ipsilateral carotid artery. As a control group, the right external jugular veins in dogs that had not received grafts were used. In the chymase inhibitor-treated group, the vein was infiltrated with 10 mu mol/L Suc-Val-Pro-Phep(OPh)2 and was grafted to the carotid artery. In the placebo-treated group, ACE activity in the grafted veins was significantly lower than that in the control veins up to 7 days after the operation, whereas chymase activity was increased significantly. After 7 days, the mRNA levels of collagen I, collagen III, and fibronectin, all of which are induced by an increase of angiotensin II action, were significantly increased in the grafted veins, and the intima-media ratio of the grafted veins was also increased. In the chymase inhibitor-treated group, the chymase activity in the grafted veins 7 days after the operation was suppressed to 12.1%. The elevated mRNA levels of fibronectin, collagen I, and collagen III in the grafted veins were significantly suppressed by treatment with the chymase inhibitor, and the intima-media ratio was also decreased significantly. Conclusions-We demonstrate for the first time that chymase-dependent angiotensin II formation plays an important role in the development of vascular proliferation in the grafted veins.

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