Cyclic GMP-dependent protein kinase expression in coronary arterial smooth muscle in response to balloon catheter injury
Cyclic GMP-dependent protein kinase expression in coronary arterial smooth muscle in response to balloon catheter injury
复制标题
DOI：
10.1161/01.atv.20.10.2192
复制
发表时间：
2000-10-01
影响因子：
8.7
通讯作者：
Lincoln, TM
中科院分区：
文献类型：
--
作者：
Anderson, PG;Boerth, NJ;Lincoln, TM
动脉平滑肌细胞在球囊导管损伤后发生表型和增殖变化。在培养细胞的研究中，一氧化氮(NO)和环鸟苷酸(CGMP)参与了抑制血管平滑肌细胞增殖和表型改变的研究。我们检测了猪冠状动脉球囊导管损伤后，平滑肌中主要的cGMP受体蛋白cGMP依赖的蛋白激酶I(PKG)的表达。损伤后新生内膜与中膜相比，PKG的表达有一过性下降。在表达细胞外基质蛋白骨桥蛋白的增殖细胞群体中观察到PKG表达的减少，但在培养液中未损伤部分的细胞中没有观察到PKG的表达。与损伤后新生内膜细胞PKG表达抑制相一致的是，新生内膜细胞中II型一氧化氮合酶(诱导型一氧化氮合酶，NOS-II)的表达显著增加，这些结果表明，在积极增殖和产生细胞外基质蛋白的冠状动脉平滑肌细胞群中，PKG的表达在损伤后一过性降低。根据iNOS的表达和我们目前对PKG在培养细胞表型调控中的作用的了解，PKG的表达减少也与损伤血管中炎症活动的增加存在时间上的相关性，这些结果表明PKG也可能调节体内血管平滑肌细胞的表型变化。
Arterial smooth muscle cells undergo phenotypic and proliferative changes in response to balloon catheter injury. Nitric oxide (NO) and cGMP have been implicated in the inhibition of vascular smooth muscle cell proliferation and phenotypic modulation in cultured-cell studies. We have examined the expression of the major cGMP receptor protein in smooth muscle, cGMP-dependent protein kinase I (PKG), in response to balloon catheter injury in the swine coronary artery. On injury, there was a transient decrease in the expression of PKG in neointimal smooth muscle cells when compared with medial smooth muscle cells. The decrease in PKG expression was observed in the population of proliferating cells expressing the extracellular matrix protein osteopontin but not in cells present in the uninjured portion of the media. Coincident with the suppression of PKG expression in neointimal cells after injury, there was a marl;ed increase in the expression of type II NO synthase (inducible NOS [iNOS], NOS-II) in the neointimal cells, These results suggest that PKG expression is transiently reduced in response to injury in the population of coronary arterial smooth muscle cells that are actively proliferating and producing extracellular matrix proteins. The reduction in PKG expression is also correlated temporally with increases in inflammatory activity in the injured vessels as assessed by iNOS expression Coupled with our current knowledge regarding the role of PKG in the regulation of cultured cell phenotypes, these results imply that PKG may also regulate phenotypic modulation of vascular smooth muscle cells in vivo as well.