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Detection of a High Ratio of Soluble to Membrane-Bound LOX-1 in Aspirated Coronary Thrombi From Patients With ST-Segment-Elevation Myocardial Infarction.

J Am Heart Assoc. 2020 Jan 21;9(2):e014008. doi:10.1161/JAHA.119.014008. Epub 2020 Jan 13
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摘要


Background The circulating level of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) is a valuable biomarker of acute myocardial infarction (AMI). The most electronegative low-density lipoprotein, L5, signals through LOX-1 to trigger atherogenesis. We examined the characteristics of LOX-1 and the role of L5 in aspirated coronary thrombi of AMI patients. Methods and Results Intracoronary thrombi were aspirated by performing interventional thrombosuction in patients with ST-segment-elevation myocardial infarction (STEMI; n=32) or non-ST-segment-elevation myocardial infarction (n=12). LOX-1 level and the ratio of sLOX-1 to membrane-bound LOX-1 were higher in thrombi of STEMI patients than in those of non-ST-segment-elevation myocardial infarction patients. In all aspirated thrombi, LOX-1 colocalized with apoB100. When we explored the role of L5 in AMI, deconvolution microscopy showed that particles of L5 but not L1 (the least electronegative low-density lipoprotein) quickly formed aggregates prone to retention in thrombi. Treating human monocytic THP-1 cells with L5 or L1 showed that L5 induced cellular adhesion and promoted the differentiation of monocytes into macrophages in a dose-dependent manner. In a second cohort of AMI patients, the L5 percentage and plasma concentration of sLOX-1 were higher in STEMI patients (n=33) than in non-ST-segment-elevation myocardial infarction patients (n=25), and sLOX-1 level positively correlated with L5 level in AMI patients. Conclusions The level of LOX-1 and the ratio of sLOX-1 to membrane-bound LOX-1 in aspirated thrombi, as well as the circulating level of sLOX-1 were higher in STEMI patients than in non-ST-segment-elevation myocardial infarction patients. L5 may play a role in releasing a high level of sLOX-1 into the circulation of STEMI patients.

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