Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Front Immunol. 2024 Apr 15;15:1383505. doi: 10.3389/fimmu.2024.1383505. eCollection 2024.
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 (MI) 导致心肌受影响区域的组织损伤。最初的炎症反应对残余心功能的损害最大,而在后期阶段,炎症是适当愈合和瘢痕形成的前提。因此,平衡 MI 后各阶段炎症的程度和持续时间对于保护心脏功能至关重要。最近,一种信号淋巴细胞激活分子 1 (SLAMF1) 衍生肽 (P7) 被证明可减少炎症细胞因子的分泌,并可预防急性脂多糖诱导的小鼠死亡。在本研究中,我们通过永久性结扎左前降支 (LAD) 在小鼠中实验性诱导 MI,并探索了立即给予 P7 的有益效果,旨在抑制初始炎症阶段而不影响愈合和重塑阶段。在 LAD 手术后 9 小时和 P7 给药时采集的血液样本可抑制炎症细胞因子的分泌,但 P7 的这种抑制作用在 3 天后减弱。超声心动图显示接受 P7 治疗的小鼠心脏收缩恶化程度较低。与此一致的是,在 P7 治疗的小鼠中观察到的心肌损伤较少。总之,在诱导 MI 后立即给予 SLAMF1 衍生肽 (P7) 可减少初始心肌炎症、减少梗死面积扩张,并导致心脏收缩恶化程度降低。