Shen Xiaozhu, Dong Nan, Xu Yiwen, Han Lin, Yang Rui, Liao Juan, Zhang Xianxian, Xie Tao, Wang Yugang, Chen Chen, Liu Mengqian, Jiang Yi, Yu Liqiang, Fang Qi
Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Geriatrics, Lianyungang Second People's Hospital, Lianyungang, China.
Front Aging Neurosci. 2022 May 9;14:863489. doi: 10.3389/fnagi.2022.863489. eCollection 2022.
The incidence of atrial fibrillation (AF)-related stroke increases with aging. Natriuretic peptides (NPs) family, including Corin-B type natriuretic peptide (BNP)-neprilysin (NEP) protein levels increased with age and are risk markers of cardiovascular and cerebrovascular diseases, such as AF and cardioembolic stroke. Aging is also linked to epigenetics, specifically DNA methylation. However, only a few studies have investigated the effect of DNA methylation on the NP system. Thus, the present study aimed to investigate whether the Corin-BNP-NEP protein pathway is involved in the pathogenesis of AF-stroke and CpG methylation in the promoter region of the Corin protein gene has an effect on AF-related ischemic stroke.
A total of 82 patients hospitalized with acute ischemic strokes were enrolled in this study. The differences in clinical information were compared between the AF-stroke ( = 37) and no AF-stroke groups ( = 45). Plasma-soluble Corin and NEP were detected using an ELISA kit. CpG methylation in the promoter region of the gene was assessed by a next-generation sequencing-based bisulfite sequencing polymerase chain reaction (BSP).
(1) Patients in AF-stroke were older, had higher initial NIHSS score, 90-day mRs, higher D2-dimer, INR, and APTT, and low TG, TC, and HbA1c (all < 0.05). (2) Serum levels of Corin and BNP in the AF-stroke group were significantly higher than that in the no AF-stroke group ( < 0.05). No significant difference was detected in the serum levels of NEP between the two groups. (3) The levels of CpG methylation in the promoter region of the Corin protein gene in the AF-stroke group was significantly lower than that in the no AF-stroke group ( < 0.05). The CpG sites with maximal methylation differences between the two groups were CORIN:678, CORIN:682, CORIN:694, and CORIN:700.
The current findings raise the possibility that the Corin-BNP-NEP protein pathway may be involved in the pathogenesis of AF-related ischemic stroke. Deficient CpG methylation in the promoter region of the Corin protein gene is associated with AF-related ischemic stroke.
心房颤动（AF）相关卒中的发病率随年龄增长而增加。利钠肽（NPs）家族，包括Corin - B型利钠肽（BNP）-中性内肽酶（NEP）蛋白水平随年龄增长而升高，是心血管和脑血管疾病（如AF和心源性栓塞性卒中）的风险标志物。衰老还与表观遗传学有关，特别是DNA甲基化。然而，仅有少数研究探讨了DNA甲基化对NP系统的影响。因此，本研究旨在探讨Corin - BNP - NEP蛋白通路是否参与AF - 卒中的发病机制，以及Corin蛋白基因启动子区域的CpG甲基化是否对AF相关缺血性卒中产生影响。
本研究共纳入82例急性缺血性卒中住院患者。比较AF - 卒中组（n = 37）和非AF - 卒中组（n = 45）的临床信息差异。使用ELISA试剂盒检测血浆可溶性Corin和NEP。通过基于下一代测序的亚硫酸氢盐测序聚合酶链反应（BSP）评估基因启动子区域的CpG甲基化。
（1）AF - 卒中组患者年龄更大，初始美国国立卫生研究院卒中量表（NIHSS）评分、90天改良Rankin量表（mRs）更高，D - 二聚体、国际标准化比值（INR）和活化部分凝血活酶时间（APTT）更高，而甘油三酯（TG）、总胆固醇（TC）和糖化血红蛋白（HbA1c）更低（均P < 0.05）。（2）AF - 卒中组的Corin和BNP血清水平显著高于非AF - 卒中组（P < 0.05）。两组间NEP血清水平未检测到显著差异。（3）AF - 卒中组Corin蛋白基因启动子区域的CpG甲基化水平显著低于非AF - 卒中组（P < 0.05）。两组间甲基化差异最大的CpG位点为CORIN:678、CORIN:682、CORIN:694和CORIN:700。
目前的研究结果提示，Corin - BNP - NEP蛋白通路可能参与AF相关缺血性卒中的发病机制。Corin蛋白基因启动子区域CpG甲基化不足与AF相关缺血性卒中有关。
