Leukocyte-Associated Immunoglobulin-like Receptor-1 is regulated in human myocardial infarction but its absence does not affect infarct size in mice

Abstract

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.

Leukocyte Associated Immunoglobulin Like Receptor 1 Regulation and Function on Monocytes and Dendritic Cells During Inflammation

“…Since an exacerbated inflammatory response might be potentially harmful, the control of the pro-inflammatory mechanisms by an anti-inflammatory counterbalance is an important protective process against further enhancement of inflammation (50,51). Our different in vitro and in vivo models indicate that inflammation leads to an upregulation of LAIR-1, as observed here in monocytes from sepsis patients, but also on circulating monocytes in acute myocardial infarction, rheumatoid arthritis and liver cirrhosis (52)(53)(54). The upregulation of LAIR-1 during inflammation, for instance mediated by TLR or IFN signals, will facilitate its inhibitory signals.…”

Integrated bioinformatics analysis reveals novel key biomarkers in diabetic nephropathy

“…Recent studies have demonstrated that the expression of TNFSF14, 54 ITGAL (integrin subunit alpha L), 55 PLAC8, 56 ADRA2A, 57 CCL21, 58 ALOX5, 59 CNR2, 60 COL1A1, 61 WNT7A, 62 SLAMF1, 63 CD3D, 64 lactotransferrin (LTF), 65 MIR27B, 66 PDK4, 67 UCN3, 68 PCK1, 69 carboxyl ester lipase (CEL), 70 TRPM6, 71 microsomal triglyceride transfer protein (MTTP), 72 CYP2 C8, 73 and CYP3A4 74 is associated with progression of type 2 diabetes mellitus. Recent studies have proposed that the altered expression of MZB1, 75 LAIR1, 76 MIR142, 77 and fibroblast activation protein alpha (FAP) 78 has been shown to be a meaningful advance factor for myocardial infarction. IRF4 plays a key role in obesity-induced insulin resistance.…”

Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in diabetic nephropathy

“…TNFSF14 [47], ITGAL (integrin subunit alpha L) [48], PLAC8 [49], ADRA2A [50], CCL21 [51], ALOX5 [52], CNR2 [53], COL1A1 [54], WNT7A [55], SLAMF1 [56], CD3D [57], LTF (lactotransferrin) [58], MIR27B [59], PDK4 [60], UCN3 [61], PCK1 [62], CEL (carboxyl ester lipase) [63], TRPM6 [64], MTTP (microsomal triglyceride transfer protein) [65], CYP2C8 [66] and CYP3A4 [67] have important role in the progression of type 2 diabetes via in ammation , but these genes might be crucial role in DN progression. Zhang et al [68], Ellenbroek et al [69], Guo et al [70] and Tillmanns et al [71] have shown that MZB1, LAIR1, MIR142 and FAP ( broblast activation protein alpha) modulating mitochondrial function and alleviating in ammation in myocardial infarction, but these genes might be involved in progression of DN. IRF4 plays a key role in the obesity-induced insulin resistance [72], but this gene might be responsible for development of DN.…”