Time-of-day variation in complement activation and endothelial glycocalyx nanomechanics in ST-elevation myocardial...

Time-of-day variation in myocardial infarction onset and ischemia-reperfusion injury is well established, but whether complement activation and the endothelial glycocalyx in ST-elevation myocardial infarction (STEMI) show temporal organization remains unclear. This study evaluated whether complement activation and endothelial glycocalyx nanomechanics in STEMI exhibit time-of-day structure and relate to short-term clinical outcomes. Endothelial glycocalyx height and stiffness and cortical stiffness were quantified in vitro using nanoindentation of human umbilical vein endothelial cells incubated with patient serum, not measured directly in patients. These measures, together with syndecan-1, C3a, C5a, left ventricular ejection fraction (LVEF), and discharge duration, were analyzed by blood sampling time in 63 first-onset STEMI patients undergoing emergency percutaneous coronary intervention, using 6-hour bins, 24-hour cosinor modeling, and multivariable analysis. Morning sampling (06:00-<12:00) showed higher cortical stiffness, syndecan-1, C3a, and C5a, and lower in vitro glycocalyx height and stiffness versus afternoon and evening; LVEF did not differ between bins. Cosinor analysis identified early-morning acrophases for cortical stiffness, syndecan-1, C3a, and C5a, with opposing evening acrophases for in vitro glycocalyx height and stiffness; troponin and C-reactive protein showed no time-of-day pattern. Principal component analysis identified a dominant component along which in vitro glycocalyx disruption and complement activation aligned with prolonged hospitalization, while preserved in vitro glycocalyx nanomechanics aligned with higher LVEF. Complement activation and endothelial glycocalyx nanomechanics in STEMI are structured across the 24-hour day, reflecting time-of-day variation. Clock time is thus a physiologically relevant variable for interpreting endothelial vulnerability in acute myocardial infarction, generating hypotheses for glycocalyx-preserving and complement-modulating strategies.