背景:动脉粥样硬化,作为心血管疾病核心的主要病理机制,现在被广泛认为与DNA损伤和修复有关,有助于动脉粥样硬化斑块的形成。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起重要作用。我们的研究努力探索参与DNA修复的特定和相关分子的贡献(APE1,BRCA1,ERCC2,miR-221-3p,miR-145-5p,和miR-155-5p)对动脉粥样硬化斑块的发展及其相互作用。
结果:使用实时聚合酶链反应(qRT-PCR)方法对50例诊断为冠心病和颈动脉疾病的患者的颈动脉粥样硬化斑块和非动脉粥样硬化内乳动脉进行基因表达研究。此外,包括50名健康对照用于测定8-羟基-2'-脱氧鸟苷(8-OHdG)。尽管在mRNA基因表达中没有观察到差异,我们注意到miR-155-5p基因表达减少(p=0.003)和miR-221-3p基因表达增加(p=0.015),而miR-145-5p基因表达保持不变(p=0.57)。关于血清8-OHdG水平,患者的水平(1111.82±28.64)明显高于对照组(636.23±24.23)(p<0.0001).
结论:在我们的研究中证明了miR-155-5p和miR-221-3p在动脉粥样硬化中的作用,我们认为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。
BACKGROUND: 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.
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).
CONCLUSIONS: 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.