Aims: Remote ischemic conditioning (RIC) alleviates ischemia-reperfusion injury via several pathways, including micro-RNAs (miRs) expression and oxidative stress modulation. We investigated the effects of RIC on endothelial glycocalyx, arterial stiffness, LV remodelling, and the underlying mediators within the vasculature as a target for protection. Methods & Results: We block-randomised 270 patients within 48h of STEMI post-PCI to either one or two cycles of bilateral brachial cuff inflation, and a control group without RIC. We measured: a) the perfusion boundary region (PBR) of the sublingual arterial microvessels to assess glycocalyx integrity; b) the carotid-femoral pulse wave velocity (PWV); c) miR-144,-150,-21,-208, nitrate-nitrite (NOx) and malondialdehyde (MDA) plasma levels at baseline (T0) and 40 minutes after RIC onset (T3); and d) LV volumes at baseline and after one year. Compared to baseline, there was a greater PBR and PWV decrease, miR-144 and NOx levels increase (p<0.05) at T3 following single-than double-cycle inflation (PBR:ΔT0-T3=0.249±0.033 vs 0.126±0.034 μm, p=0.03 and PWV:0.4±0.21 vs -1.02±0.24 m/s, p=0.03). and reduced MDA was observed after both protocols. Increased miR-144 was related with PWV reduction (r=0.763, p<0.001) after the first-cycle inflation in both protocols. After one year, single-cycle RIC was associated with LV end-systolic volume reduction (LVESV) >15% (odds-ratio of 3.75,p=0.029). miR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up (r=0.40 and 0.37, p<0.05), in the single cycle RIC. Conclusion: RIC evokes "vascular conditioning" likely by upregulation of cardio-protective microRNAs, NOx production, and oxidative stress reduction, facilitating reverse LV remodelling.
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