EXPRESS: Longitudinal Circulating miRNA Profiling Identifies Pharmacodynamic Biomarkers of Remote Ischemic...

Remote ischemic conditioning(RIC) is a promising neuroprotective strategy for ischemic stroke, but reliable pharmacodynamic biomarkers confirming its biological activity are lacking. In this translational sub-study of the multicenter randomized phase II TRICS-9 trial, we profiled five circulating microRNAs (miR-181b,miR-150,miR-143,miR-223, and let-7a) in 42 acute stroke patients assigned to RIC or standard medical therapy at 24 hours and 72 hours post-randomization.At 24 hours, miR-143,miR-150, and let-7a were significantly lower in RIC patients, with miR-143 and miR-150 showing strong pharmacodynamic biomarker performance in receiver operating characteristic analysis. At 72 hours, miR-181b was significantly elevated in RIC patients, while let-7a and miR-223 remained suppressed.Longitudinal paired analysis revealed significant within-patient temporal increases in miR-181b,miR-150, and miR-143 from 24 to 72 hours in RIC patients consistent with a biphasic molecular response to conditioning. These findings identify miR-143, miR-150, let-7a, and miR-181b as candidate pharmacodynamic biomarkers of RIC biological activity. Importantly, none of the candidate miRNAs demonstrated significant correlation with stroke severity, discharge NIHSS, or 90-day functional outcome, consistent with their role as pharmacodynamic rather than prognostic markers. These results provide mechanistic support for translational convergence between preclinical and clinical RIC neuroprotection research and highlight the need for external validation in larger outcome-linked cohorts.