A miRNA signature linked to high lipoprotein (a) and coronary calcification in familial hypercholesterolaemia.

IF 4.1 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Computational and structural biotechnology journal Pub Date : 2025-09-17 eCollection Date: 2025-01-01 DOI:10.1016/j.csbj.2025.09.026
Rafael Escate, Juan F Sánchez Muñoz-Torrero, Marta Mauri, Pedro Mata, Lina Badimon, Teresa Padro
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引用次数: 0

Abstract

Background: High lipoprotein(a) [Lp(a)] levels are associated with increased coronary artery calcification (CAC) in familial hypercholesterolaemia (FH) patients. However, mechanisms linking high Lp(a) with CAC remain poorly understood. In this study, we have performed a bioinformatics and system biology analysis to identify miRNAs and their target genes involved in Lp(a)-associated atherosclerotic lesion and coronary calcification in FH patients.

Methods: Patients with a genetic diagnosis of FH (n = 24) from the SAFEHEART were included in the study. Plasma miRNA signature was obtained using Affymetrix miRNA microarrays from patients with FH grouped using an Lp(a) cut-off of (>50 mg/dL) and presence or absence of coronary artery calcification [CCS(+) or CCS(-)]. In silico analyses were performed to identify potential miRNA target genes.

Results: Forty-two miRNAs had > 1.5-fold difference in their detection levels when grouped by Lp(a) [FH-Lp(a)> 50 (n = 9) vs FH-Lp(a)< 50 (n = 15)]. Among these, 9 miRNAs were associated with CCS(+) (miR-1228-5p, miR-3940-5p, miR-1237-5p, miR-3196, miR-6765-5p, miR-6786-5p, miR-4486, miR-6821-5p and miR-1908-5p). In silico analysis, identified 68 target genes of these 9 miRNAs in lipid and atherosclerosis pathways (KEGG code: hsa05417). Network analysis revealed seven target genes (AKT3, APAF1, BCL2L1, TRAF6, MYD88, STAT3, and CASP9) with stronger interactions and higher binding probability for the nine-miRNA signature, mainly linked to lipid metabolism, inflammation and calcification processes.

Conclusion: Our results identify a miRNA signature that regulates atherosclerotic processes associated with high Lp(a) levels and CAC in asymptomatic FH patients. These findings offer new insights into the underlying mechanisms and highlight potential therapeutic targets.

家族性高胆固醇血症中与高脂蛋白(A)和冠状动脉钙化相关的miRNA特征
背景:家族性高胆固醇血症(FH)患者的高脂蛋白(a) [Lp(a)]水平与冠状动脉钙化(CAC)增加有关。然而,高Lp(a)与CAC之间的联系机制仍然知之甚少。在这项研究中,我们进行了生物信息学和系统生物学分析,以确定FH患者Lp(a)相关动脉粥样硬化病变和冠状动脉钙化相关的mirna及其靶基因。方法:从SAFEHEART中纳入遗传诊断为FH的患者(n = 24)。使用Affymetrix miRNA微阵列获得FH患者的血浆miRNA特征,使用Lp(a)截止值(>50 mg/dL)和冠状动脉钙化是否存在[CCS(+)或CCS(-)]进行分组。通过计算机分析鉴定潜在的miRNA靶基因。结果:42种mirna按Lp(a)分组时,其检测水平有> 1.5倍的差异[FH-Lp(a)> 50 (n = 9)vs FH-Lp(a)n = 15)]。其中,9个mirna与CCS(+)相关(miR-1228-5p、miR-3940-5p、miR-1237-5p、miR-3196、miR-6765-5p、miR-6786-5p、miR-4486、miR-6821-5p和miR-1908-5p)。通过计算机分析,鉴定出这9种mirna在脂质和动脉粥样硬化途径中的68个靶基因(KEGG代码:hsa05417)。网络分析显示,7个靶基因(AKT3、APAF1、BCL2L1、TRAF6、MYD88、STAT3和CASP9)对9 - mirna特征具有较强的相互作用和较高的结合概率,主要与脂质代谢、炎症和钙化过程有关。结论:我们的研究结果确定了在无症状FH患者中调节与高Lp(a)水平和CAC相关的动脉粥样硬化过程的miRNA特征。这些发现为潜在的机制提供了新的见解,并突出了潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Computational and structural biotechnology journal
Computational and structural biotechnology journal Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
9.30
自引率
3.30%
发文量
540
审稿时长
6 weeks
期刊介绍: Computational and Structural Biotechnology Journal (CSBJ) is an online gold open access journal publishing research articles and reviews after full peer review. All articles are published, without barriers to access, immediately upon acceptance. The journal places a strong emphasis on functional and mechanistic understanding of how molecular components in a biological process work together through the application of computational methods. Structural data may provide such insights, but they are not a pre-requisite for publication in the journal. Specific areas of interest include, but are not limited to: Structure and function of proteins, nucleic acids and other macromolecules Structure and function of multi-component complexes Protein folding, processing and degradation Enzymology Computational and structural studies of plant systems Microbial Informatics Genomics Proteomics Metabolomics Algorithms and Hypothesis in Bioinformatics Mathematical and Theoretical Biology Computational Chemistry and Drug Discovery Microscopy and Molecular Imaging Nanotechnology Systems and Synthetic Biology
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