The transcription factor ETS-1 mediates proinflammatory responses and neointima formation in carotid artery endoluminal vascular injury.
The transcription factor ETS-1 mediates proinflammatory responses and neointima formation in carotid artery endoluminal vascular injury.
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DOI：
10.1161/hypertensionaha.110.150995
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Jaimes EA
中科院分区：
文献类型：
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作者：
Feng W;Xing D;Hua P;Zhang Y;Chen YF;Oparil S;Jaimes EA
转录因子ETS-1是高血压血管炎症和肥大的关键介质。我们检验了ETS-1是颈动脉球囊损伤后促炎反应和新生内膜增生的介质的假设。在这项研究中，我们利用了ETS-1显性阴性（DN）肽的可用性。将Sprague-Dawley大鼠分配用ETS-1 DN、突变肽（ETS-1 MU）或媒介物（Veh）处理，并使其经受颈动脉的球囊损伤。在2、24小时和14天后，对大鼠实施安乐死，并对两个颈动脉进行实时聚合酶链反应（2小时）、免疫荧光和免疫组织化学（24小时）以及形态测定分析（14天）。ETS-1 mRNA在损伤的颈动脉中上调（2.4倍）。通过免疫荧光，我们证实了ETS-1在损伤后24小时的核表达增加。损伤后2 h，颈动脉单核细胞趋化蛋白-1、中性粒细胞趋化因子-2、P-选择素、E-选择素、血管细胞粘附分子和细胞间粘附分子的mRNA表达增加。ETS-1 DN（但不是ETS-1 MU）显着降低损伤动脉中单核细胞趋化蛋白-1、P-选择素和E-选择素的mRNA和蛋白表达。这些变化伴随着血管单核细胞和白细胞浸润的减少。此外，用ETS-1 DN而不是ETS-1 MU治疗导致球囊损伤后第14天新生内膜形成减少50%。本研究揭示了ETS-1作为炎症介质和颈动脉球囊损伤模型中新生内膜形成的作用，并可能导致血管损伤治疗新策略的发展。
The transcription factor ETS-1 is a critical mediator of vascular inflammation and hypertrophy in hypertension. We tested the hypothesis that ETS-1 is a mediator of proinflammatory responses and neointimal hyperplasia after balloon injury of the carotid artery. For this study, we took advantage of the availability of an ETS-1 dominant-negative (DN) peptide. Sprague-Dawley rats were assigned to treatment with ETS-1 DN, a mutant peptide (ETS-1 MU), or vehicle (Veh) and subjected to balloon injury of the carotid artery. After 2, 24 hours, and 14 days, the rats were euthanized, and both carotid arteries were processed for real-time polymerase chain reaction (2 hours), immunofluorescence and immunohistochemistry (24 hours), and morphometric analysis (14 days). ETS-1 mRNA was up regulated (2.4-fold) in injured carotid arteries. By immunofluorescence, we confirmed increased nuclear expression of ETS-1 24 hours postinjury. The carotid artery mRNA expression of monocyte chemotactic protein-1, cytokine-induced neutrophil chemoattractant-2, P-selectin, E-selectin, vascular cell adhesion molecule, and intercellular adhesion molecule was increased 2 hours after injury. ETS-1 DN but not ETS-1 MU significantly reduced mRNA and protein expression for monocyte chemotactic protein-1, P-selectin, and E-selectin in injured arteries. These changes were accompanied by concomitant reductions in vascular monocyte and leukocyte infiltration. Moreover, treatment with ETS-1 DN but not ETS-1 MU resulted in a 50% reduction in neointima formation at day 14 after balloon injury. This study unveils the role of ETS-1 as a mediator of inflammation and neointima formation in a model of carotid artery balloon injury and may result in the development of novel strategies in the treatment of vascular injury.