Department of Cardiovascular Surgery Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.
Department of Medical Biology, Cerrahpasa Medicine Faculty, Istanbul University-Cerrahpasa, Istanbul, 34098, Turkey.
Mol Biol Rep. 2024 Sep 4;51(1):953. doi: 10.1007/s11033-024-09886-8.
Atherosclerosis, serving as the primary pathological mechanism at the core of cardiovascular disease, is now widely acknowledged to be associated with DNA damage and repair, contributing to atherosclerotic plaque formation. Therefore, molecules involved in the DNA repair process may play an important role in the progression of atherosclerosis. Our research endeavors to explore the contributions of specific and interrelated molecules involved in DNA repair (APE1, BRCA1, ERCC2, miR-221-3p, miR-145-5p, and miR-155-5p) to the development of atherosclerotic plaque and their interactions with each other.
METHODS & RESULTS: Gene expression study was conducted using the real-time polymerase chain reaction (qRT-PCR) method on samples from carotid artery atherosclerotic plaques and nonatherosclerotic internal mammary arteries obtained from 50 patients diagnosed with coronary artery disease and carotid artery disease. Additionally, 50 healthy controls were included for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Although no difference was observed in mRNA gene expressions, we noted a decrease in miR-155-5p gene expression (p = 0.003) and an increase in miR-221-3p gene expression (p = 0.015) in plaque samples, while miR-145-5p gene expression remained unchanged (p = 0.57). Regarding serum 8-OHdG levels, patients exhibited significantly higher levels (1111.82 ± 28.64) compared to controls (636.23 ± 24.23) (p < 0.0001).
In our study demonstrating the role of miR-155-5p and miR-221-3p in atherosclerosis, we propose that these molecules are potential biomarkers and therapeutic targets for coronary artery diseases and carotid artery disease.
动脉粥样硬化作为心血管疾病的主要病理机制核心，现已广泛认为与 DNA 损伤和修复有关，导致动脉粥样硬化斑块形成。因此，参与 DNA 修复过程的分子可能在动脉粥样硬化的进展中发挥重要作用。我们的研究旨在探讨特定和相互关联的 DNA 修复分子（APE1、BRCA1、ERCC2、miR-221-3p、miR-145-5p 和 miR-155-5p）对动脉粥样硬化斑块发展的贡献及其相互作用。
使用实时聚合酶链反应 (qRT-PCR) 方法对 50 例经冠状动脉疾病和颈动脉疾病诊断的患者颈动脉粥样硬化斑块和非动脉粥样硬化内乳动脉样本进行基因表达研究，并对 50 例健康对照者进行 8-羟基-2'-脱氧鸟苷 (8-OHdG) 测定。尽管 mRNA 基因表达没有差异，但我们注意到斑块样本中 miR-155-5p 基因表达下降（p=0.003），miR-221-3p 基因表达升高（p=0.015），而 miR-145-5p 基因表达不变（p=0.57）。关于血清 8-OHdG 水平，患者明显高于对照组（1111.82±28.64比 636.23±24.23）（p<0.0001）。
在我们的研究中，miR-155-5p 和 miR-221-3p 在动脉粥样硬化中的作用表明，这些分子是冠状动脉疾病和颈动脉疾病的潜在生物标志物和治疗靶点。
