Beta-Secretase-1 Antisense RNA Is Associated with Vascular Ageing and Atherosclerotic Cardiovascular Disease

Bampatsias, Dimitrios and Mavroeidis, Ioannis and Tual-Chalot, Simon and Vlachogiannis, Nikolaos I and Bonini, Francesca and Sachse, Marco and Mavraganis, Georgios and Mareti, Alexia and Kritsioti, Chrysoula and Laina, Ageliki and Delialis, Dimitrios and Ciliberti, Giorgia and Sopova, Kateryna and Gatsiou, Aikaterini and Martelli, Fabio and Georgiopoulos, Georgios and Stellos, Konstantinos and Stamatelopoulos, Kimon (2022) Beta-Secretase-1 Antisense RNA Is Associated with Vascular Ageing and Atherosclerotic Cardiovascular Disease. Thrombosis and Haemostasis, 122 (11). pp. 1932-1942. ISSN 0340-6245

Abstract

Background The noncoding antisense transcript for β-secretase-1 (BACE1-AS) is a long noncoding RNA with a pivotal role in the regulation of amyloid-beta; (Abeta;). We aimed to explore the clinical value of BACE1-AS expression in atherosclerotic cardiovascular disease (ASCVD). Methods Expression of BACE1-AS and its target, beta;-secretase 1 (BACE1) mRNA, was measured in peripheral blood mononuclear cells derived from 434 individuals (259 without established ASCVD [non-CVD], 90 with stable coronary artery disease [CAD], and 85 with acute coronary syndrome). Intima-media thickness and atheromatous plaques evaluated by ultrasonography, as well as arterial wave reflections and pulse wave velocity, were measured as markers of subclinical ASCVD. Patients were followed for a median of 52 months for major adverse cardiovascular events (MACE). Results In the cross-sectional arm, BACE1-AS expression correlated with BACE1 expression (r.0.396, p<0.001) and marginally with Abeta;1.40 levels in plasma (r.0.141, p.0.008). Higher BACE1-AS was associated with higher estimated CVD risk assessed by HeartScore for non-CVD subjects and by European Society of Cardiology clinical criteria for the total population (p<0.05 for both). BACE1-AS was associated with higher prevalence of CAD (odds ratio [OR]=1.85, 95% confidence interval [CI]: 1.37-2.5), multivessel CAD (OR=1.36, 95% CI: 1.06-1.75), and with higher number of diseased vascular beds (OR=1.31, 95% CI: 1.07-1.61, for multiple diseased vascular beds) after multivariable adjustment for traditional cardiovascular risk factors. In the prospective arm, BACE1-AS was an independent predictor of MACE in high cardiovascular risk patients (adjusted hazard ratio=1.86 per ascending tertile, 95% CI: 1.011-3.43, p=0.046). Conclusion BACE1-AS is associated with the incidence and severity of ASCVD.