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miR33-5p 和 ABCA1 在冠心病患者外周血单个核细胞中的表达及其作用

Involvement of Expression of miR33-5p and ABCA1 in Human Peripheral Blood Mononuclear Cells in Coronary Artery Disease.

机构信息

Phisiology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1. Col. Sección XVI, Mexico City 14380, Mexico.

Endocrinology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1. Col. Sección XVI, Mexico City 14380, Mexico.

出版信息

Int J Mol Sci. 2024 Aug 7;25(16):8605. doi: 10.3390/ijms25168605.

Abstract

MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression post-transcriptionally and are crucial in lipid metabolism. ATP-binding cassette transporter A1 (ABCA1) is essential for cholesterol efflux from cells to high-density lipoprotein (HDL). Dysregulation of miRs targeting can affect cholesterol homeostasis and contribute to coronary artery disease (CAD). This study aimed to investigate the expression of miRs targeting in human monocytes, their role in cholesterol efflux, and their relationship with CAD. We included 50 control and 50 CAD patients. RT-qPCR examined the expression of miR-33a-5p, miR-26a-5p, and miR-144-3p in monocytes. Logistic regression analysis explored the association between these miRs and CAD. HDL's cholesterol acceptance was analyzed using the J774A.1 cell line. Results showed that miR-26a-5p ( = 0.027) and ( = 0.003) expression levels were higher in CAD patients, while miR-33a-5p ( < 0.001) levels were lower. Downregulation of miR-33a-5p and upregulation of were linked to a lower CAD risk. Atorvastatin upregulated mRNA, and metformin downregulated miR-26a-5p in CAD patients. Decreased cholesterol efflux correlated with higher CAD risk and inversely with miRs in controls. Reduced miR-33a-5p expression and increased expression are associated with decreased CAD risk. miR deregulation in monocytes may influence atherosclerotic plaque formation by regulating cholesterol efflux. Atorvastatin and metformin could offer protective effects by modulating miR-33a-5p, miR-26a-5p, and , suggesting potential therapeutic strategies for CAD prognosis and treatment.

摘要

微小 RNA(miRs)是一种小的非编码 RNA,可在后转录水平上调节基因表达,在脂质代谢中至关重要。三磷酸腺苷结合盒转运体 A1(ABCA1)是胆固醇从细胞向高密度脂蛋白(HDL)流出的必需物质。针对 的 miRs 的失调会影响胆固醇稳态,并导致冠状动脉疾病(CAD)。本研究旨在研究人类单核细胞中针对 的 miRs 的表达、它们在胆固醇流出中的作用以及它们与 CAD 的关系。我们纳入了 50 名对照和 50 名 CAD 患者。RT-qPCR 检测了单核细胞中 miR-33a-5p、miR-26a-5p 和 miR-144-3p 的表达。逻辑回归分析探讨了这些 miRs 与 CAD 之间的关系。使用 J774A.1 细胞系分析了 HDL 的胆固醇摄取。结果表明,CAD 患者的 miR-26a-5p( = 0.027)和 ( = 0.003)表达水平更高,而 miR-33a-5p 水平更低( < 0.001)。miR-33a-5p 的下调和 的上调与 CAD 风险降低相关。阿托伐他汀上调 CAD 患者的 mRNA,二甲双胍下调 miR-26a-5p。胆固醇流出减少与 CAD 风险增加相关,而在对照组中与 miRs 呈负相关。miR-33a-5p 表达降低和 表达增加与 CAD 风险降低相关。单核细胞中 miR 的失调可能通过调节胆固醇流出影响动脉粥样硬化斑块的形成。阿托伐他汀和二甲双胍可能通过调节 miR-33a-5p、miR-26a-5p 和 ,提供对 CAD 预后和治疗的保护作用,从而提供潜在的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0de/11354752/cc34f9567631/ijms-25-08605-g001.jpg

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