Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts; Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts.
J Am Coll Cardiol. 2020 Mar 3;75(8):901-915. doi: 10.1016/j.jacc.2019.12.056.
Recurrent myocardial infarction (MI) is common in patients with coronary artery disease and is associated with high mortality. Long-term reprogramming of myeloid progenitors occurs in response to inflammatory stimuli and alters the organism's response to secondary inflammatory challenges.
This study examined the effect of recurrent MI on bone marrow response and cardiac inflammation.
The investigators developed a surgical mouse model in which 2 subsequent MIs affected different left ventricular regions in the same mouse. Recurrent MI was induced by ligating the left circumflex artery followed by the left anterior descending coronary artery branch. The study characterized the resulting ischemia by whole-heart fluorescent coronary angiography after optical organ clearing and by cardiac magnetic resonance imaging.
A first MI-induced bone marrow "memory" via a circulating signal, reducing hematopoietic maintenance factor expression in bone marrow macrophages. This dampened the organism's reaction to subsequent events. Despite a similar extent of injury according to troponin levels, recurrent MI caused reduced emergency hematopoiesis and less leukocytosis than a first MI. Consequently, fewer leukocytes migrated to the ischemic myocardium. The hematopoietic response to lipopolysaccharide was also mitigated after a previous MI. The increase of white blood count in 28 patients was lower after recurrent MI compared with their first MI.
The data suggested that hematopoietic and innate immune responses are shaped by a preceding MI.
复发性心肌梗死（MI）在冠心病患者中很常见，与高死亡率相关。髓系祖细胞在长期的炎症刺激下发生重编程，改变了机体对二次炎症挑战的反应。
本研究旨在探讨复发性 MI 对骨髓反应和心脏炎症的影响。
研究人员建立了一种手术小鼠模型，其中 2 次 MI 影响同一小鼠的不同左心室区域。通过结扎左回旋支动脉，然后结扎左前降支冠状动脉分支来诱导复发性 MI。通过光学器官清除后的全心脏荧光冠状动脉造影和心脏磁共振成像来描述由此产生的缺血情况。
首次 MI 通过循环信号产生骨髓“记忆”，降低骨髓巨噬细胞中造血维持因子的表达，从而抑制了机体对后续事件的反应。尽管根据肌钙蛋白水平，两次 MI 造成的损伤程度相似，但复发性 MI 导致的紧急造血减少和白细胞增多症比首次 MI 要少。因此，向缺血心肌迁移的白细胞较少。先前的 MI 也会减轻对脂多糖的造血反应。与首次 MI 相比，28 例患者的白细胞计数增加较低。
数据表明，造血和先天免疫反应受到先前 MI 的影响。
