Haematology Research Unit, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia.
Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Centre for Heart Research, Westmead Institute for Medical Research, Westmead, NSW, Australia.
Pathology. 2022 Feb;54(1):87-94. doi: 10.1016/j.pathol.2021.05.099. Epub 2021 Sep 4.
Cardiovascular disease, including myocardial infarction (MI), is the leading cause of death globally. Current antithrombotic medications used during MI treatment are predominantly directed towards platelet inhibition and, to a lesser extent, anticoagulation. Bleeding is a major risk of such treatment and could be circumvented by targeting other causative factors essential for arterial thrombus formation. We sought to re-evaluate the cellular composition of arterial thrombus in order to better understand mechanisms that lead to coronary artery thrombosis in acute MI. We performed detailed histological and immunohistochemical analysis of coronary artery thrombi aspirated from 26 patients undergoing emergency percutaneous coronary intervention for acute ST elevated myocardial infarction (STEMI). Coronary arterial thrombi had an unanticipated cellular heterogeneity. Neutrophil extracellular traps (NETs) were observed in thrombi as identified by anti-citrullinated histone 3 and anti-myeloperoxidase staining. Increased abundance of NETs was seen directly surrounding erythrocytes. Extracellular iron and erythrocyte fragments were also associated with areas of NETs suggesting a possible link. Our results shed light on potential involvement of erythrocytes in coronary arterial thrombosis through activation of platelets and induction of NETs. If supported by further in vitro and in vivo studies, novel therapies to inhibit NET formation or coagulation activation by erythrocyte release products, could bolster current myocardial infarction treatment.
心血管疾病，包括心肌梗死（MI），是全球范围内的主要死亡原因。目前在 MI 治疗中使用的抗血栓药物主要针对血小板抑制，在较小程度上针对抗凝。出血是此类治疗的主要风险，通过针对动脉血栓形成的其他必需致病因素，可以避免出血。我们试图重新评估动脉血栓的细胞组成，以便更好地了解导致急性 MI 冠状动脉血栓形成的机制。我们对 26 名因急性 ST 段抬高型心肌梗死（STEMI）而行紧急经皮冠状动脉介入治疗的患者进行了冠状动脉血栓抽吸，并对其进行了详细的组织学和免疫组织化学分析。冠状动脉血栓具有出乎意料的细胞异质性。通过抗瓜氨酸化组蛋白 3 和抗髓过氧化物酶染色鉴定，在血栓中观察到中性粒细胞胞外诱捕网（NETs）。NETs 的丰度增加直接围绕着红细胞。细胞外铁和红细胞碎片也与 NETs 区域相关，表明可能存在联系。我们的结果表明，红细胞通过激活血小板和诱导 NETs，可能参与了冠状动脉血栓形成。如果得到进一步的体外和体内研究的支持，针对 NET 形成或红细胞释放产物的凝血激活的新型治疗方法，可能会增强当前的心肌梗死治疗。
