Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Sci Rep. 2017 Dec 21;7(1):18039. doi: 10.1038/s41598-017-13678-5.
Heart failure after myocardial infarction (MI) depends on infarct size and adverse left ventricular (LV) remodelling, both influenced by the inflammatory response. Leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) is an inhibitory receptor of ITAM-dependent cell activation, present on almost all immune cells. We investigated regulation of LAIR-1 leukocyte expression after MI in patients and hypothesized that its absence in a mouse model of MI would increase infarct size and adverse remodelling. In patients, LAIR-1 expression was increased 3 days compared to 6 weeks after MI on circulating monocytes (24.8 ± 5.3 vs. 21.2 ± 5.1 MFI, p = 0.008) and neutrophils (12.9 ± 4.7 vs. 10.6 ± 3.1 MFI, p = 0.046). In WT and LAIR-1 mice, infarct size after ischemia-reperfusion injury was comparable (37.0 ± 14.5 in WT vs. 39.4 ± 12.2% of the area at risk in LAIR-1, p = 0.63). Remodelling after permanent left coronary artery ligation did not differ between WT and LAIR-1 mice (end-diastolic volume 133.3 ± 19.3 vs. 132.1 ± 27.9 μL, p = 0.91 and end-systolic volume 112.1 ± 22.2 vs. 106.9 ± 33.5 μL, p = 0.68). Similarly, no differences were observed in inflammatory cell influx or fibrosis. In conclusion, LAIR-1 expression on monocytes and neutrophils is increased in the acute phase after MI in patients, but the absence of LAIR-1 in mice does not influence infarct size, inflammation, fibrosis or adverse cardiac remodelling.
心肌梗死后的心力衰竭（HF）取决于梗死面积和不良的左心室（LV）重构，这两者均受炎症反应的影响。白细胞相关免疫球蛋白样受体 1（LAIR-1）是一种 ITAM 依赖性细胞激活的抑制性受体，几乎存在于所有免疫细胞上。我们研究了 MI 后患者白细胞中 LAIR-1 表达的调节，并假设在 MI 的小鼠模型中缺乏 LAIR-1 会增加梗死面积和不良重构。在患者中，与 MI 后 6 周相比，MI 后 3 天循环单核细胞（24.8 ± 5.3 与 21.2 ± 5.1 MFI，p = 0.008）和中性粒细胞（12.9 ± 4.7 与 10.6 ± 3.1 MFI，p = 0.046）中 LAIR-1 的表达增加。在 WT 和 LAIR-1 小鼠中，缺血再灌注损伤后的梗死面积相当（WT 中为 37.0 ± 14.5%，LAIR-1 中为 39.4 ± 12.2%的危险区域，p = 0.63）。永久性左冠状动脉结扎后的重构在 WT 和 LAIR-1 小鼠之间没有差异（舒张末期容积 133.3 ± 19.3 与 132.1 ± 27.9 μL，p = 0.91 和收缩末期容积 112.1 ± 22.2 与 106.9 ± 33.5 μL，p = 0.68）。同样，在炎症细胞浸润或纤维化方面也没有观察到差异。总之，患者 MI 后急性期单核细胞和中性粒细胞上的 LAIR-1 表达增加，但在小鼠中缺乏 LAIR-1 并不影响梗死面积、炎症、纤维化或不良的心脏重构。
