Endothelial cells overexpressing interleukin-8 receptors reduce inflammatory and neointimal responses to arterial injury.
Endothelial cells overexpressing interleukin-8 receptors reduce inflammatory and neointimal responses to arterial injury.
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DOI：
10.1161/circulationaha.111.078436
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发表时间：
2012-03-27
期刊：
影响因子：
37.8
通讯作者：
Chen YF
中科院分区：
文献类型：
--
作者：
Xing D;Li P;Gong K;Yang Z;Yu H;Hage FG;Oparil S;Chen YF
中性粒细胞膜上的白细胞介素-8（IL 8）受体IL 8 RA和IL 8 RB与IL 8结合，并将中性粒细胞募集到炎症部位，包括急性损伤的动脉。本研究测试了施用IL 8 RA和/或IL 8 RB转导的大鼠主动脉内皮细胞（EC）是否加速EC粘附至损伤表面，从而抑制球囊损伤的大鼠颈动脉中的炎症和新生内膜形成。我们测试了这样的假设，即通过过表达IL 8 RA和RB受体靶向递送EC可以预防炎症反应并促进腔内损伤后动脉的结构恢复。年轻成年雄性大鼠接受右颈动脉的球囊损伤，并静脉输注用携带IL 8 RA、IL 8 RB、IL 8 RA/RB（双转导）基因的腺病毒载体转导的EC（在损伤后1、3和5小时总共1.5×106个细胞）、Adhesion（空载体）或媒介物（无EC输注）。过度表达IL 8 R的EC显著抑制促炎介质表达（60-85%），并在损伤后1天减少中性粒细胞和单核细胞/巨噬细胞向损伤动脉中的浸润，以及在损伤后14天刺激再内皮化增加2倍。IL 8 RA-EC、IL 8 RB-EC和IL 8 RA/RB-EC处理在损伤后28天显著减少新生内膜形成（减少80%、74%和95%）。具有IL 8 RA和/或IL 8 RB过表达的EC模拟靶向并粘附于受损组织的嗜中性粒细胞的行为，从而防止炎症和新生内膜形成。将内皮细胞靶向输送到有腔内损伤的动脉为预防和治疗心血管疾病提供了一种新的策略。
Interleukin-8 (IL8) receptors IL8RA and IL8RB on neutrophil membranes bind to IL8 and direct neutrophil recruitment to sites of inflammation, including acutely injured arteries. This study tested whether administration of IL8RA- and/or IL8RB-transduced rat aortic endothelial cells (ECs) accelerates adhesion of ECs to the injured surface, thus suppressing inflammation and neointima formation in balloon injured rat carotid arteries. We tested the hypothesis that targeted delivery of ECs by overexpressing IL8RA and RB receptors prevents inflammatory responses and promotes structural recovery of arteries following endoluminal injury. Young adult male rats received balloon injury of the right carotid artery and were transfused i.v. with ECs (total 1.5×106 cells at 1, 3, and 5 hrs post injury) transduced with adenoviral vectors carry IL8RA, IL8RB, IL8RA/RB (dual transduction) genes, AdNull (empty vector), or vehicle (no EC transfusion). ECs overexpressing IL8Rs inhibited pro-inflammatory mediators expression significantly (by 60–85%) and reduced infiltration of neutrophils and monocytes/macrophages into injured arteries at 1 day post injury, as well as stimulating a 2-fold increase in re-endothelialization at 14 days post injury. IL8RA-EC, IL8RB-EC, and IL8RA/RB-EC treatment reduced neointima formation dramatically (by 80%, 74%, and 95%) at 28 days post injury. ECs with overexpression of IL8RA and/or IL8RB mimic the behavior of neutrophils that target and adhere to injured tissues, preventing inflammation and neointima formation. Targeted delivery of ECs to arteries with endoluminal injury provides a novel strategy for the prevention and treatment of cardiovascular disease.