新生内膜
血红素加氧酶
血管成形术
狭窄
免疫印迹
动脉
内生
药理学
医学
一氧化氮
气球
污渍
化学
内科学
酶
血红素
生物化学
再狭窄
支架
基因
作者
David A. Tulis,William Durante,Kelly J. Peyton,Gary B. Chapman,Alida J. Evans,Andrew I. Schafer
标识
DOI:10.1006/bbrc.2000.3942
摘要
The pathobiologic process of arterial stenosis following balloon angioplasty continues to be an enigmatic problem in clinical settings. This research project investigates the ability of YC-1, a benzyl indazole derivative that sensitizes sGC/cGMP, to stimulate endogenous cGMP and attenuate balloon injury-induced neointima (NI) formation in the rat carotid artery. Northern and Western blot analyses revealed enhanced acute expression of iNOS and inducible heme oxygenase (HO-1) mRNA and protein in the injured artery. The contralateral uninjured artery also demonstrated acute HO-1 mRNA and protein induction without detectable iNOS expression. Perivascular application of YC-1 immediately following injury significantly stimulated acute vessel wall cGMP compared to untreated controls. YC-1 treated sections demonstrated significant reduction in NI area (-74%), NI area/medial wall area (-72%), and NI thickness (-76%) 2 weeks post-injury. These results directly implicate YC-1 as a potent new therapeutic agent capable of reducing post-angioplasty stenosis through endogenous CO- and/or NO-mediated, cGMP-dependent processes.
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