Reducing In-Stent Restenosis: Therapeutic Manipulation of miRNA in Vascular Remodeling and Inflammation.
Reducing In-Stent Restenosis: Therapeutic Manipulation of miRNA in Vascular Remodeling and Inflammation.
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DOI：
10.1016/j.jacc.2015.03.549
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发表时间：
2015-06-02
影响因子：
24
通讯作者：
Baker AH
中科院分区：
文献类型：
--
作者：
McDonald RA;Halliday CA;Miller AM;Diver LA;Dakin RS;Montgomery J;McBride MW;Kennedy S;McClure JD;Robertson KE;Douglas G;Channon KM;Oldroyd KG;Baker AH
药物洗脱支架降低了支架内再狭窄的发生率，但它们导致动脉愈合延迟，并与慢性炎症反应和超敏反应相关。确定新的干预措施，以促进伤口愈合和减少炎症反应可能会改善长期的临床结果。微核糖核酸（Micro-ribonucleic acids，miRNAs）是一类非编码的小分子核糖核酸，在血管损伤后炎症的发生和消退中起重要作用。本研究旨在确定植入裸金属和药物洗脱支架后miRNA的调节和功能。采用猪、小鼠和体外模型研究miRNA在支架内再狭窄中的作用。我们记录了猪支架植入后激活的炎性miRNAs的子集，包括miR-21茎环miRNAs。miR-21干环的基因消融减弱了小鼠支架植入后的新生内膜形成。这是通过抗炎M2巨噬细胞水平的提高以及平滑肌细胞对血管激活的敏感性受损而发生的。MiR-21在促进支架损伤后的血管炎症和重塑中起着重要作用。miRNA介导的支架植入后炎症反应的调节可能具有加速伤口愈合和增强支架植入临床疗效的治疗潜力。
Drug-eluting stents reduce the incidence of in-stent restenosis, but they result in delayed arterial healing and are associated with a chronic inflammatory response and hypersensitivity reactions. Identifying novel interventions to enhance wound healing and reduce the inflammatory response may improve long-term clinical outcomes. Micro–ribonucleic acids (miRNAs) are noncoding small ribonucleic acids that play a prominent role in the initiation and resolution of inflammation after vascular injury. This study sought to identify miRNA regulation and function after implantation of bare-metal and drug-eluting stents. Pig, mouse, and in vitro models were used to investigate the role of miRNA in in-stent restenosis. We documented a subset of inflammatory miRNAs activated after stenting in pigs, including the miR-21 stem loop miRNAs. Genetic ablation of the miR-21 stem loop attenuated neointimal formation in mice post-stenting. This occurred via enhanced levels of anti-inflammatory M2 macrophages coupled with an impaired sensitivity of smooth muscle cells to respond to vascular activation. MiR-21 plays a prominent role in promoting vascular inflammation and remodeling after stent injury. MiRNA-mediated modulation of the inflammatory response post-stenting may have therapeutic potential to accelerate wound healing and enhance the clinical efficacy of stenting.