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Circulating miR-6821-5p levels and coronary calcification in asymptomatic familial hypercholesterolemia patients.
- Source :
-
Atherosclerosis [Atherosclerosis] 2024 May; Vol. 392, pp. 117502. Date of Electronic Publication: 2024 Mar 08. - Publication Year :
- 2024
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Abstract
- Background and Aims: Premature atherosclerotic cardiovascular disease (CVD) is a clinic characteristic of familial hypercholesterolemia (FH). Coronary calcium score (CCS) is a highly used imaging modality to evidence atherosclerotic plaque burden. microRNAs (miRNAs) are non-coding RNAs that epigenetically regulate gene expression. Here, we investigated whether CCS associates with a specific miRNA-signature in FH-patients.<br />Methods: Patients with genetic diagnosis of FH (N = 86) from the nationwide SAFEHEART-cohort were investigated by computed tomography angiography imaging and classified depending on the presence of coronary calcification in FH-CCS (+) and FH-CCS (-) groups by the Agatston score. Differential miRNA profiling was performed in two stages: first by Affymetrix microarray technology (high-throughput differential profiling-studies) and second by RT-PCR using TaqMan-technology (analytical RT-qPCR study) in plasma of the two patient groups.<br />Results: miR-193a-5p, miR-30e-5p and miR-6821-5p levels were significantly higher in FH-CCS (+) compared to FH-CCS (-). miR-6821-5p was the best miRNA to discriminate FH-patients CCS(+), according to receiver operating characteristic (ROC) analysis (AUC: 0.70 ± 0.06, p = 0.006). High miR-6821-5p levels were associated with older age (p = 0.03) and high LDL-burden (p = 0.014) using a ROC-derived cut-off value. However, miR-6821-5p did not correlate with age in either the CCS- or CCS + group. Genes involved in calcification processes were identified by in silico analysis. The relation of cell-calcification and expression levels of miR-6821-5p, BMP2 and SPP1 was validated experimentally in human vascular smooth muscle cell cultures.<br />Conclusions: Up-regulated levels of miR-6821-5p are found in the plasma of asymptomatic FH-patients with coronary calcified atherosclerotic plaques, as well as in isolated human vascular smooth muscle cells expressing the pro-calcification genes BMP2 and SPP1. These findings highlight the impact of epigenetic regulation on the development of subclinical atherosclerosis.<br />Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LB declares to have acted as SAB member of Sanofi, Ionnis, Pfizer and NovoNordisk; to have a Research Grant of AstraZeneca; to have received speaker fees from Sanofi and Bayer and to have founded the Spin-offs Glycardial Diagnostics SL and Ivastatin Therapeutics SL (all unrelated to this work). TP declares to be co-founder of the Spin-offs Glycardial Diagnostics SL and Ivastatin Therapeutics SL (all unrelated to this work). The remaining authors have nothing to disclose.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Male
Female
Middle Aged
Adult
Asymptomatic Diseases
Computed Tomography Angiography
Circulating MicroRNA blood
Circulating MicroRNA genetics
Coronary Angiography
Cells, Cultured
Plaque, Atherosclerotic blood
Biomarkers blood
Gene Expression Profiling
Aged
Myocytes, Smooth Muscle metabolism
Coronary Vessels diagnostic imaging
Coronary Vessels pathology
ROC Curve
Hyperlipoproteinemia Type II blood
Hyperlipoproteinemia Type II genetics
Hyperlipoproteinemia Type II complications
Coronary Artery Disease blood
Coronary Artery Disease genetics
Coronary Artery Disease diagnostic imaging
Vascular Calcification blood
Vascular Calcification genetics
Vascular Calcification diagnostic imaging
MicroRNAs blood
MicroRNAs genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1484
- Volume :
- 392
- Database :
- MEDLINE
- Journal :
- Atherosclerosis
- Publication Type :
- Academic Journal
- Accession number :
- 38513437
- Full Text :
- https://doi.org/10.1016/j.atherosclerosis.2024.117502