Fedorov Anton, Kostareva Anna, Raud Johan, Roy Joy, Hedin Ulf, Razuvaev Anton
Institute of Molecular Biology and Genetics, Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg, Russia; Ariadne Genomics, Rockville, Maryland.
Institute of Molecular Biology and Genetics, Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg, Russia; Women's and Children's Health, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
J Vasc Interv Radiol. 2014 May;25(5):789-796.e7. doi: 10.1016/j.jvir.2013.11.031. Epub 2014 Feb 6.
Restenosis caused by intimal hyperplasia (IH) remains a significant drawback for vascular interventions. It is crucial to understand the molecular mechanisms that control activation of smooth muscle cells (SMCs) after the injury in order to develop strategies to prevent IH. The purpose of the present study was to investigate the early alterations in arterial-wall gene expression after balloon injury in the rat carotid artery with focus on the induction of an inflammatory response.
Twenty-four male Sprague-Dawley rats were subjected to injury of the left common carotid artery by using a 2-F Fogarty catheter. The arteries were harvested 5, 10, and 20 hours after injury. Uninjured arteries from an additional eight rats were used as controls. RNA was isolated and used for genome-wide microarray expression analysis, followed by validation of selected genes with quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed on the cross-sectioned vessels.
Analysis of gene expression by microarrays showed that the most differentially expressed genes were primarily associated with inflammation, cell proliferation, migration, and adhesion. As confirmed by qRT-PCR, microarray data showed a significant (P < .005) upregulation of cytokines and chemokines (IL-6, CCL2, CXCL1, AIMP1, and CD44) just 5 hours after injury. Immunohistochemistry demonstrated that CCL2 and the adhesion receptor CD44 were expressed by SMCs in the early response to injury and in the absence of leukocyte infiltration.
Arterial injury is followed by an early induction of inflammatory genes in the vessel wall that appears to be confined to SMCs.
内膜增生（IH）导致的再狭窄仍然是血管介入治疗的一个重大缺陷。了解损伤后控制平滑肌细胞（SMC）激活的分子机制对于制定预防IH的策略至关重要。本研究的目的是调查大鼠颈动脉球囊损伤后动脉壁基因表达的早期变化，重点是炎症反应的诱导。
24只雄性Sprague-Dawley大鼠用2F Fogarty导管对左颈总动脉进行损伤。在损伤后5、10和20小时采集动脉。另外8只大鼠的未损伤动脉用作对照。分离RNA并用于全基因组微阵列表达分析，随后用定量实时聚合酶链反应（qRT-PCR）验证选定基因。对横切血管进行免疫组织化学分析。
微阵列基因表达分析表明，差异表达最显著的基因主要与炎症、细胞增殖、迁移和黏附有关。qRT-PCR证实，微阵列数据显示损伤后仅5小时细胞因子和趋化因子（IL-6、CCL2、CXCL1、AIMP1和CD44）就有显著（P <.005）上调。免疫组织化学表明，CCL2和黏附受体CD44在损伤早期反应中由SMC表达，且无白细胞浸润。
动脉损伤后血管壁早期诱导炎症基因，且似乎局限于SMC。
