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

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 p < 0.001), as well as NO concentration (p < 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: p < 0.001/heparan sulfate: p < 0.001/hyaluronic acid: p < 0.0001). A D2B > 60 min led to the pronounced loss of eGC height/stiffness (both, p < 0.001) with reduced NO concentrations (p < 0.01), activated the complement system (p < 0.001), and prolonged the hospital stay (p < 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.

Dysregulated complement activation during acute myocardial infarction leads to endothelial glycocalyx degradation and endothelial dysfunction via the C5a:C5a-Receptor1 axis

“…During AMI, the main constituents of the eGC can be detected in patients’ blood. Syndecan-1 ( 36 ), heparan sulfate ( 12 ), and hyaluronan ( 37 ) have been identified as biomarkers for eGC damage during myocardial ischemia. This also applies to our data.…”

“…Particularly, the mechanisms underlying complement-mediated injury to the myocardium mediated by the late components of the complement system’s terminal pathway have previously been characterized ( 9 – 11 ). However, dysregulated complement activation causes not only myocardial damage, but also damage to the vascular endothelium ( 12 , 13 ). Although the terminal pathway seems to play an important role in the development of endothelial damage during dysregulated complement activation, little attention has been paid to the effect of the anaphylatoxin C5a ( 14 ).…”