Clark James E, Dudler Thomas, Marber Michael S, Schwaeble Wilhelm
BHF Centre, School of Cardiovascular Medicine and Sciences, King's College London, London, UK.
Drug Discovery, Omeros Corporation, Seattle, Washington, USA.
Open Heart. 2018 Jan 9;5(1):e000652. doi: 10.1136/openhrt-2017-000652. eCollection 2018.
Myocardial ischaemia-reperfusion injury is a major cause of mortality and morbidity in the developed world. Many approaches have been investigated to counteract the pathological consequences associated with acute myocardial infarction (AMI) and cardiac remodelling. It is accepted that inflammation, and therefore activation of the complement pathway, is a crucial step in the pathogenesis of this injury, and many attempts have been made to ameliorate the infarction and consequent dysfunction using anticomplement therapy, with mixed success. Recently, the lectin complement activation pathway involving the mannose-binding lectin-associated serine protease 2 (MASP-2) has been shown to be an important mediator of the inflammatory response in ischaemia/reperfusion injury in the heart. In this study, therefore, we aimed to investigate the feasibility of using monoclonal antibodies raised against MASP-2 in a murine model of AMI.
Mice were injected with anti-MASP-2 antibody or control 18 hours prior to experimental infarction by ligation of the left anterior descending coronary artery for 30 min followed by 120 min reperfusion. The developed infarct was measured, and blood was collected for analysis of lectin pathway functional activity.
We found that mice treated with anti-MASP-2 antibody had smaller infarcts than those treated with control antibody. We believe this may represent a valuable step forward in the protection of the myocardium against ischaemia-reperfusion injury.
心肌缺血再灌注损伤是发达国家死亡率和发病率的主要原因。人们已经研究了许多方法来对抗与急性心肌梗死（AMI）和心脏重塑相关的病理后果。炎症以及补体途径的激活被认为是这种损伤发病机制中的关键步骤，并且已经进行了许多尝试使用抗补体疗法来改善梗死和随之而来的功能障碍，但结果不一。最近，涉及甘露糖结合凝集素相关丝氨酸蛋白酶2（MASP-2）的凝集素补体激活途径已被证明是心脏缺血/再灌注损伤中炎症反应的重要介质。因此，在本研究中，我们旨在研究在AMI小鼠模型中使用针对MASP-2产生的单克隆抗体的可行性。
在通过结扎左冠状动脉前降支30分钟然后再灌注120分钟进行实验性梗死前18小时，给小鼠注射抗MASP-2抗体或对照。测量形成的梗死面积，并收集血液用于分析凝集素途径功能活性。
我们发现用抗MASP-2抗体治疗的小鼠梗死面积比用对照抗体治疗的小鼠小。我们认为这可能是在保护心肌免受缺血再灌注损伤方面向前迈出的有价值的一步。
