MICA: Developmental clinical studies- Effect of elafin on myocardial injury and inflammation in coronary artery bypass surgery

MICA：发育性临床研究 - elafin 对冠状动脉搭桥手术中心肌损伤和炎症的影响

• 批准号: G1001339/1
• 负责人: Peter Henriksen
• 金额: $ 44.87万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1001339%2F1
• 关键词: MICA; Developmental; clinical; studies; Effect

Heart muscle cells are susceptible to injury and death following interruption of blood flow (myocardial ischaemia). A mild form of injury occurs during coronary artery bypass surgey and can be measured using a sensitive blood marker (troponin) providing a helpful model to study drugs that may reduce ischaemic injury. Neutrophils are circulating blood cells that contribute to ischaemic injury by releasing destructive enzymes (elastases). Humans produce a protein called elafin that reduces neutrophil elastase injury. Extensive preclinical work from different international centres indicates that elafin has a therapeutic role in diseases of the arteries and heart characterised by neutrophil mediated injury. We believe that administering elafin to patients undergoing bypass surgery will reduce neutrophil mediated myocardial injury and the rise in post-operative inflammatory activity. The degree of heart muscle damage occurring during ischaemia determines clinical outcomes. No therapies are available to address neutrophil mediated heart muscle injury and development of a drug to reduce this offers substantial clinical benefit.

心肌细胞在血流中断（心肌缺血）后易受损伤和死亡。在冠状动脉搭桥手术中发生轻度损伤，可以使用敏感的血液标记物（肌钙蛋白）进行测量，为研究可能减少缺血性损伤的药物提供了有用的模型。中性粒细胞是通过释放破坏性酶（弹性蛋白酶）而导致缺血性损伤的循环血细胞。人类产生一种称为弹性蛋白的蛋白质，可以减少中性粒细胞弹性蛋白酶的损伤。来自不同国际中心的广泛临床前工作表明，弹性蛋白酶在以中性粒细胞介导的损伤为特征的动脉和心脏疾病中具有治疗作用。我们相信，给予接受搭桥手术的患者弹性蛋白酶将减少中性粒细胞介导的心肌损伤和术后炎症活动的增加。缺血期间发生的心肌损伤程度决定了临床结局。没有治疗方法可用于解决中性粒细胞介导的心肌损伤，并且开发药物以减少这种损伤提供了实质性的临床益处。