Department of Cardiovascular Surgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, China.
Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Epigenetics. 2024 Dec;19(1):2392400. doi: 10.1080/15592294.2024.2392400. Epub 2024 Aug 21.
Even though N6-methyladenosine (m6A) RNA modifications are increasingly being implicated in human disease, their mechanisms are not fully understood in smokers with coronary artery disease (CAD). Thirty m6A-related regulators' expression (MRRE) in CAD individuals (smokers and non-smokers) were analyzed from GEO. Support Vector Machine, random forest, and nomogram models were constructed to assess its clinical value. Consensus clustering, principal component analysis, and ssGSEA were used to construct a full picture of m6A-related regulators in smokers with CAD. Oxygen-glucose deprivation (OGD) and qRT-PCR were used to validate hypoxia's effect on MRRE. A comparison between smokers with CAD and controls revealed lower expression levels of RBM15B, YTHDC2, and ZC3H13. Based on three key MRREs, all models showed good clinical value, and smokers with CAD were divided into two distinct molecular subgroups. The correlations were found between key MRRE and the degree of immune infiltration. Three key MRREs in HUVECs and FMC84 mouse cardiomyocytes were reduced in the OGD group. Through hypoxia, smoking might reduce the expression levels of RBM15B, YTHDC2, and ZC3H13 in smokers with CAD. Our findings provide an important theoretical basis for the treatment of smokers with CAD.
尽管 N6-甲基腺苷(m6A)RNA 修饰在人类疾病中越来越受到关注,但在患有冠心病(CAD)的吸烟者中,其机制尚不完全清楚。从 GEO 分析了 CAD 个体(吸烟者和非吸烟者)中的 30 个 m6A 相关调节剂表达(MRRE)。构建了支持向量机、随机森林和列线图模型来评估其临床价值。共识聚类、主成分分析和 ssGSEA 用于构建吸烟者 CAD 中 m6A 相关调节剂的全貌。氧葡萄糖剥夺(OGD)和 qRT-PCR 用于验证低氧对 MRRE 的影响。CAD 吸烟者与对照组之间的比较显示 RBM15B、YTHDC2 和 ZC3H13 的表达水平较低。基于三个关键的 MRRE,所有模型都显示出良好的临床价值,并将 CAD 吸烟者分为两个不同的分子亚群。关键的 MRRE 与免疫浸润程度之间存在相关性。在 HUVEC 和 FMC84 小鼠心肌细胞中,三个关键的 MRRE 在 OGD 组中减少。通过低氧,吸烟可能会降低 CAD 吸烟者中 RBM15B、YTHDC2 和 ZC3H13 的表达水平。我们的研究结果为治疗 CAD 吸烟者提供了重要的理论基础。