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Beta-secretase-1 antisense RNA is associated with vascular ageing and atherosclerotic cardiovascular disease

Lookup NU author(s): Dr Simon Tual-Chalot, Dr Nikolaos Vlachogiannis, Dr Kateryna Sopova, Dr Aikaterini GatsiouORCiD, Dr Georgios Georgiopoulos, Professor Konstantinos StellosORCiD, Professor Kimon Stamatelopoulos

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 2022 Georg Thieme Verlag. All rights reserved. Background and aims: The non-coding antisense transcript for beta-secretase-1 (BACE1-AS) is a long non-coding RNA with a pivotal role in the regulation of amyloid-beta (Aβ). 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 (PBMCs) 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 cardiac events (MACE). Results: In the cross-sectional arm, BACE1-AS expression correlated with BACE1 expression (r=0.396, p<0.001) and marginally with Aβ1-40 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 ESC clinical criteria for the total population (p<0.05 for both). BACE1-AS was associated with higher prevalence of CAD [OR=1.85 (95% 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 HR= 1.86 per ascending tertile, (95% CI: 1.011-3.43), p=0.046]. Conclusions: BACE1-AS is associated with the incidence and severity of ASCVD.


Publication metadata

Author(s): Bampatsias D, Mavroeidis I, Tual-Chalot S, Vlachogiannis NL, Bonini F, Sachse M, Mavraganis G, Mareti A, Kritsioti C, Laina A, Delialis D, Ciliberti G, Sopova K, Gatsiou A, Martelli F, Georgiopoulos G, Stellos K, Stamatelopoulos K

Publication type: Article

Publication status: Published

Journal: Thrombosis and Haemostasis

Year: 2022

Pages: Epub ahead of print

Online publication date: 01/08/2022

Acceptance date: 05/07/2022

Date deposited: 23/09/2022

ISSN (print): 0340-6245

ISSN (electronic): 2567-689X

Publisher: Georg Thieme Verlag

URL: https://doi.org/10.1055/a-1914-2094

DOI: 10.1055/a-1914-2094

PubMed id: 35915966


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Funding

Funder referenceFunder name
101016072
23054
75732319
759248
GGP19035
RF-2019-12368521

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