@article{3076315, title = "Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study", author = "Ikonomidis, I. and Vlastos, D. and Andreadou, I. and Gazouli, M. and Efentakis, P. and Varoudi, M. and Makavos, G. and Kapelouzou, A. and Lekakis, J. and Parissis, J. and Katsanos, S. and Tsilivarakis, D. and Hausenloy, D.J. and Alexopoulos, D. and Cokkinos, D.V. and Bøtker, H.-E. and Iliodromitis, E.K.", journal = "Basic Research in Cardiology", year = "2021", volume = "116", number = "1", publisher = "Springer Science and Business Media Deutschland GmbH", issn = "0300-8428, 1435-1803", doi = "10.1007/s00395-021-00851-1", keywords = "acetylsalicylic acid; beta adrenergic receptor blocking agent; clopidogrel; dipeptidyl carboxypeptidase inhibitor; enoxaparin; heparin; hydroxymethylglutaryl coenzyme A reductase inhibitor; malonaldehyde; microRNA; miR 144; miR 150; miR 208; miR 21; nitrate; nitrite; unclassified drug; autacoid; circulating microRNA; microRNA, acute heart infarction; adult; arterial stiffness; Article; carotid-femoral pulse wave velocity; controlled study; female; glycocalyx; heart left ventricle endsystolic volume; heart left ventricle volume; heart ventricle remodeling; human; major clinical study; male; oxidative stress; percutaneous coronary intervention; randomized controlled trial; remote ischemic conditioning; ST segment elevation myocardial infarction; adverse event; aged; artery; blood; blood flow; diagnostic imaging; endothelium cell; Greece; heart left ventricle function; ischemic postconditioning; metabolism; middle aged; myocardial ischemia reperfusion injury; pathophysiology; percutaneous coronary intervention; prospective study; time factor; treatment outcome; upper limb; vascularization, Adult; Aged; Arteries; Circulating MicroRNA; Endothelial Cells; Female; Glycocalyx; Greece; Humans; Inflammation Mediators; Ischemic Postconditioning; Male; MicroRNAs; Middle Aged; Myocardial Reperfusion Injury; Oxidative Stress; Percutaneous Coronary Intervention; Prospective Studies; Regional Blood Flow; ST Elevation Myocardial Infarction; Time Factors; Treatment Outcome; Upper Extremity; Vascular Stiffness; Ventricular Function, Left; Ventricular Remodeling", abstract = "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 and results: We block-randomised 270 patients within 48 h 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 min 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). Increased miR-150,-21,-208 (p < 0.05) and reduced MDA was observed after both protocols. Increased miR-144 was related to 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. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT03984123. © 2021, Springer-Verlag GmbH, DE part of Springer Nature." }