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延长的门球时间导致ST段抬高型心肌梗死患者内皮糖萼损伤和内皮功能障碍。

Prolonged Door-to-Balloon Time Leads to Endothelial Glycocalyx Damage and Endothelial Dysfunction in Patients with ST-Elevation Myocardial Infarction.

作者信息

Vahldieck Carl, Fels Benedikt, Löning Samuel, Nickel Laura, Weil Joachim, Kusche-Vihrog Kristina

机构信息

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.

出版信息

Biomedicines. 2023 Oct 29;11(11):2924. doi: 10.3390/biomedicines11112924.

Abstract

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.

摘要

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。

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