Table_1_SLAMF1-derived peptide exhibits cardio protection after permanent left anterior descending artery ligation in mice.docx

Acute myocardial infarction (MI) results in tissue damage to affected areas of the myocardium. The initial inflammatory response is the most damaging for residual cardiac function, while at later stages inflammation is a prerequisite for proper healing and scar formation. Balancing the extent and duration of inflammation during various stages after MI is thus pivotal for preserving cardiac function. Recently, a signaling lymphocytic activation molecule 1 (SLAMF1)-derived peptide (P7) was shown to reduce the secretion of inflammatory cytokines and protected against acute lipopolysaccharide-induced death in mice. In the present study, we experimentally induced MI by permanent ligation of the left anterior descending artery (LAD) in mice and explored the beneficial effect of immediately administering P7, with the aim of dampening the initial inflammatory phase without compromising the healing and remodeling phase. Blood samples taken 9 h post-LAD surgery and P7 administration dampened the secretion of inflammatory cytokines, but this dampening effect of P7 was diminished after 3 days. Echocardiography revealed less deterioration of cardiac contraction in mice receiving P7. In line with this, less myocardial damage was observed histologically in P7-treated mice. In conclusion, the administration of a SLAMF1-derived peptide (P7) immediately after induction of MI reduces the initial myocardial inflammation, reduces infarct expansion, and leads to less deterioration of cardiac contraction.

急性心肌梗死（Acute myocardial infarction, MI）会导致受累心肌区域出现组织损伤。疾病初始阶段的炎症反应对残余心功能的损害最为显著，而在疾病后期，炎症却是实现正常愈合与瘢痕形成的先决条件。因此，在心肌梗死后的各阶段平衡炎症的程度与持续时间，对维持心功能至关重要。
近期有研究发现，一种源自信号淋巴细胞活化分子1（signaling lymphocytic activation molecule 1, SLAMF1）的肽类（P7）可抑制炎症细胞因子分泌，并可抵御脂多糖诱导的小鼠急性死亡。本研究中，我们通过对小鼠实施左前降支动脉（left anterior descending artery, LAD）永久结扎的方式构建实验性心肌梗死模型，并探究了即刻给予P7的治疗获益，旨在抑制疾病初始炎症阶段，同时不损害愈合与心室重塑进程。
在左前降支结扎手术与P7给药后9小时采集的血液样本显示，P7可抑制炎症细胞因子的分泌，但该抑制作用在给药3天后便有所减弱。超声心动图（echocardiography）检查结果表明，接受P7治疗的小鼠心脏收缩功能的恶化程度更低。与此一致，组织学检测显示P7治疗组小鼠的心肌损伤程度更轻。
综上，在心肌梗死造模后即刻给予源自SLAMF1的肽类P7，可减轻初始心肌炎症反应、缩小梗死扩展范围，并缓解心脏收缩功能的恶化。