P3204The role of microRNA expression in remote ischemic conditioning improvement of aortic elastic properties and endothelial glycocalyx integrity in acute myocardial infarction

Abstract

Background: Remote ischemic conditioning attenuates ischemia-reperfusion injury in patients with STEMI. However, its effects on vascular function and biochemical mechanisms, including microRNA (miRs) expression, are not fully defined. Methods: We examined 180 patients with STEMI and 30 healthy controls. The conditioning protocol utilised either a double (15 minute separation), or a single ischemic stimulus by brachial cuff inflation of both arms at 200mmHg for 5 min, after a baseline assessment of vascular function (T0). Each ischemic stimulus was followed by a vascular function assessment, with a final vascular assessment 25 minutes after the second cuff deflation. 20 patients underwent a sham conditioning procedure, by way of cuff inflation omission after their placement around the ordinary brachial position. In each vascular function examination we measured: a) the carotid-femoral pulse wave velocity (PWV); and b) the perfusion boundary region (PBR-micrometers) of the sublingual arterial microvessels as a marker of endothelial glycocalyx thickness. The expression of microRNA-144,-150,-499 (cardioprotective action), -21, and -208 (remodeling stimuli), as possible mediators of the conditioning mechanism, was quantified at baseline (T0) and after the last vascular function examination (T3), by polymerase chain reaction. Results: Our single cuff inflation conditioning protocol resulted in a more pronounced and statistically significant aortic elasticity improvement (PWV T0: 12.09 m/s, T1: 11.54m/s, T2: 11.39m/s, T3: 11.71m/s). Patients with baseline PWV >11 m/s benefited from an earlier and greater improvement of aortic elasticity compared to patients with lower baseline PWV at T1 (mean difference in PWV improvement= 3.5 m/s, p<0.002). Similarly, a greater glycocalyx integrity restoration was observed in patients with baseline PBR>2.1 (n=50) (mean difference in PBR improvement=0.5 at T1, p<0.001). Furthermore, there was a statistically significant increase in miR-144,-150, -499, -21, and -208 expression (55.9 vs 7.4/U6sn, p<0.001; 3.4 vs 1.8/U6sn, p<0.05, p=0.01; 3.5 vs 1.6/U6sn, p<0.001; 2.1 vs 1.2/U6sn; 2.4 vs 1.9/U6sn) compared to baseline; the increase in miR-144 expression was significantly positively linearly correlated with PWV reduction at 5 min post cuff deflation (T1 measurement r=0.763, p<0.001). None of the examined markers of vascular function or microRNA expression were affected by the sham conditioning procedure (p=ns). (Figure presented) Conclusion: Remote ischemic conditioning causes an acute short-term improvement of vascular function, likely by upregulation of cardio-protective microRNAs expression.