Abstract 16485: Treatment With PCSK9 Inhibitors Influence miRNAs Expression and Changes of Arterial Wall Properties

Abstract

Background and aim: MicroRNAs (miRNAs) are involved in the synthesis of proprotein convertase subtilisin-kexin type 9(PCSK9), which is one of regulators of low-density lipoprotein cholesterol (LDL-C) metabolism. There is no data on whether changes in the expression of miRNAs involved in PCSK9 metabolism, could be related to arterial wall properties changes. The aim was to verify whether PCSK9 inhibitors (PCSK9i) treatment and the changes in the expression of miRNAs are associated with arterial wall properties in post-myocardial infarction (MI) patients with insufficiently regulated LDL-C levels and increased Lp(a) levels. Methods: Seventy-six participants after MI were enrolled and randomized to a placebo group or PCSK9i group. The treatment group received subcutaneous alirocumab 150 mg or evolokumab 140 mg, every 2 weeks. Blood for biochemical and genetic analysis was taken and ultrasound measurements of flow-mediated dilation of brachial artery (FMD), carotid intima-media thickness (c-IMT) and pulse wave velocity (PWV) were performed. All measurements were measured initially and after 6 months of treatment. Results: FMD improved from 10.9±6.3 to 14.4±5.7% in the PCSK9i group and 10.8±6.8 to 11.2±4.6% in the placebo group (p<0.001, p=0.584). PWV changed from 5.8±1.4 to 5.5±1.6 m/s (p=0.024) in the PCSK9i group and in the placebo group from 5.6±1.5 to 5.5±1.1 m/s (p=0.879), with better improvement in the treated group (p=0.007). c-IMT decreased in the PCSK9i group (from 0.65±0.10 to 0.63±0.10 mm; p=0.017), with no change in the placebo group (from 0.64±0.09 to 0.63±0.09 mm; p=0.482). The expression of miR-191-5p and miR-483-5p increased in the PCSK9i group (p=0.028, p=0.020; respectively). The expression of miR-191-5p significantly decreased in the placebo group (p< 0.001). A decrease in c-IMT was associated with a decrease in the expression of miR-224-5p (r=0.303; p=0.019), miR-337-3p (r=0.329; p=0.010) and miR-483-5p (r=0.367; p=0.004). Conclusions: Our results suggest that changes in selected miRNAs were associated with changes in the morphological properties of the arterial vessel wall. We have shown that the increase in miR-483-5p expression can be a good indicator of the regression of morphological atherosclerotic changes.