Boerth N J, Dey N B, Cornwell T L, Lincoln T M
Department of Pathology, University of Alabama at Birmingham, 35294-0019, USA.
J Vasc Res. 1997 Jul-Aug;34(4):245-59. doi: 10.1159/000159231.
Nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP) have been reported to prevent vascular smooth muscle cell (VSMC) proliferation and have beneficial effects to reduce intimal thickening in response to arterial injury. The purpose of this study was to determine whether the downstream effector molecule of NO-cGMP signaling, cyclic GMP-dependent protein kinase (PKG), regulates phenotypic modulation and proliferation in cultured rat aortic VSMC. PKG-expressing VSMC lines were created by transfection of PKG-deficient cell lines and characterized. All forms of PKG, i.e. PKG-I alpha and PKG-I beta, as well as the constitutively active catalytic domain of PKG-I, transformed dedifferentiated 'synthetic' VSMC to a more contractile-like morphology. PKG expression resulted in an increased production of the contractile phenotype marker proteins, smooth muscle myosin heavy chain-2, calponin and alpha-actin and restored the capacity of cAMP and cGMP analogues to inhibit platelet-derived growth factor (PDGF)-induced cell migration. On the other hand, PKG expression had no significant effects on PDGF-induced cell proliferation. These results suggest that PKG expression contributes to the regulation of a contractile-like phenotypic expression in cultured VSMC, and the suppression of PKG expression during cultured growth in vitro may permit the modulation of cells to a more synthetic, dedifferentiated phenotype.
据报道，一氧化氮（NO）和环磷酸鸟苷（cGMP）可防止血管平滑肌细胞（VSMC）增殖，并对减轻动脉损伤后的内膜增厚具有有益作用。本研究的目的是确定NO-cGMP信号的下游效应分子，即环磷酸鸟苷依赖性蛋白激酶（PKG），是否调节培养的大鼠主动脉VSMC的表型调节和增殖。通过转染PKG缺陷细胞系创建并鉴定了表达PKG的VSMC系。所有形式的PKG，即PKG-Iα和PKG-Iβ，以及PKG-I的组成型活性催化结构域，都将去分化的“合成”VSMC转变为更具收缩样的形态。PKG表达导致收缩表型标记蛋白、平滑肌肌球蛋白重链-2、钙调蛋白和α-肌动蛋白的产生增加，并恢复了cAMP和cGMP类似物抑制血小板衍生生长因子（PDGF）诱导的细胞迁移的能力。另一方面，PKG表达对PDGF诱导的细胞增殖没有显著影响。这些结果表明，PKG表达有助于调节培养的VSMC中收缩样表型的表达，并且在体外培养生长过程中PKG表达的抑制可能使细胞调节为更具合成性、去分化的表型。
