Vahldieck Carl, Fels Benedikt, Löning Samuel, Nickel Laura, Weil Joachim, Kusche-Vihrog Kristina
Department of Anesthesiology and Intensive Care Medicine, University Medical Centre Schleswig-Holstein Campus Luebeck, 23538 Luebeck, Germany.
Institute of Physiology, University of Luebeck, 23562 Luebeck, Germany.
Biomedicines. 2023 Oct 29;11(11):2924. doi: 10.3390/biomedicines11112924.
Damage to the endothelial glycocalyx (eGC) has been reported during acute ischemic events like ST-elevation myocardial infarction (STEMI). In STEMI, a door-to-balloon time (D2B) of <60 min was shown to reduce mortality and nonfatal complications. Here, we hypothesize that eGC condition is associated with D2B duration and endothelial function during STEMI. One hundred and twenty-six individuals were analyzed in this study (STEMI patients vs. age-/sex-matched healthy volunteers). After stimulating endothelial cells with patient/control sera, the eGC's nanomechanical properties (i.e., height/stiffness) were analyzed using the atomic force microscopy-based nanoindentation technique. eGC components were determined via ELISA, and measurements of nitric oxide levels (NO) were based on chemiluminescence. eGC height/stiffness (both < 0.001), as well as NO concentration ( < 0.001), were reduced during STEMI. Notably, the D2B had a strong impact on the endothelial condition: a D2B > 60 min led to significantly higher serum concentrations of eGC components (syndecan-1: < 0.001/heparan sulfate: < 0.001/hyaluronic acid: < 0.0001). A D2B > 60 min led to the pronounced loss of eGC height/stiffness (both, < 0.001) with reduced NO concentrations ( < 0.01), activated the complement system ( < 0.001), and prolonged the hospital stay ( < 0.01). An increased D2B led to severe eGC shedding, with endothelial dysfunction in a temporal context. eGC components and pro-inflammatory mediators correlated with a prolonged D2B, indicating a time-dependent immune reaction during STEMI, with a decreased NO concentration. Thus, D2B is a crucial factor for eGC damage during STEMI. Clinical evaluation of the eGC condition might serve as an important predictor for the endothelial function of STEMI patients in the future.
据报道,在急性缺血事件如ST段抬高型心肌梗死(STEMI)期间,内皮糖萼(eGC)会受到损伤。在STEMI中,门球时间(D2B)<60分钟可降低死亡率和非致命性并发症。在此,我们假设eGC状况与STEMI期间的D2B持续时间和内皮功能有关。本研究分析了126名个体(STEMI患者与年龄/性别匹配的健康志愿者)。在用患者/对照血清刺激内皮细胞后,使用基于原子力显微镜的纳米压痕技术分析eGC的纳米力学特性(即高度/硬度)。通过酶联免疫吸附测定法测定eGC成分,基于化学发光法测量一氧化氮水平(NO)。在STEMI期间,eGC高度/硬度(均<0.001)以及NO浓度(<0.001)均降低。值得注意的是,D2B对内皮状况有强烈影响:D2B>60分钟导致eGC成分的血清浓度显著升高(多配体蛋白聚糖-1:<0.001/硫酸乙酰肝素:<0.001/透明质酸:<0.0001)。D2B>60分钟导致eGC高度/硬度明显丧失(均<0.001),NO浓度降低(<0.01),激活补体系统(<0.001),并延长住院时间(<0.01)。D延长导致严重的eGC脱落,并在一定时间内出现内皮功能障碍。eGC成分和促炎介质与延长的D2B相关,表明STEMI期间存在时间依赖性免疫反应,且NO浓度降低。因此,D2B是STEMI期间eGC损伤的关键因素。对eGC状况的临床评估可能在未来作为STEMI患者内皮功能的重要预测指标。