Gumanova Nadezhda G, Bogdanova Natalya L, Gorshkov Alexander Yu
Department of Biochemistry, National Research Center for Preventive Medicine (NRCPM), Moscow, Russia.
Chef of the Department of Microcirculation, National Research Center for Preventive Medicine (NRCPM), Moscow, Russia.
Horm Mol Biol Clin Investig. 2025 Feb 4. doi: 10.1515/hmbci-2024-0073.
The present study evaluated the relationships of the serum levels of the cyclic dinucleotide 2'3'-cyclic GMP-AMP (cGAMP) marker of activation of pattern-recognition receptors with immunoglobulin G antibodies against severe acute respiratory syndrome-linked coronavirus (IgG-SARS)-positive status and endothelial dysfunction.
Selected groups from two cohorts (cohort 1 of 307 healthy volunteers and cohort 2 of 218 coronary heart disease [CHD] patients). COVID-19 infection was confirmed by detection of IgG-SARS against SARS-CoV-2 S1 protein receptor-binding domain. Cohort 1 was examined for systematic coronary risk evaluation by European Society of Cardiology (SCORE) starting from 2019 before the onset of the COVID-19 pandemic. Cohort 2 was processed starting from 2017 (three years prior to the COVID-19 pandemic) in a hospital setting to undergo coronary angiography to assess coronary lesions as Gensini score. The levels of cGAMP and endothelial markers (nitrate and nitrite combined as NOx and endothelin-1) were assessed in the serum to evaluate the associations with IgG-SARS status, SCORE, and extent of coronary lesions by correlation and receiver operating characteristic analyses.
Serum cGAMP did not discriminate between SARS-positive and SARS-negative healthy subject of cohort 1. Moreover, the level of cGAMP was not associated with endothelial biomarkers in healthy subjects. However, Serum cGAMP was associated with atherosclerosis, with area under the curve 0.69 (95 % CI 0.587-0.806; p=0.001), and with endothelial markers in cohort 2.
Low cGAMP was associated with atherosclerosis in CHD patients, suggesting that cGAMP is a new biomarker in the context of sterile inflammation.
本研究评估了模式识别受体激活的环状二核苷酸2'3'-环磷酸鸟苷-腺苷酸（cGAMP）血清水平与抗严重急性呼吸综合征相关冠状病毒免疫球蛋白G抗体（IgG-SARS）阳性状态及内皮功能障碍之间的关系。
从两个队列中选取研究对象（队列1为307名健康志愿者，队列2为218名冠心病[CHD]患者）。通过检测针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）S1蛋白受体结合域的IgG-SARS来确认新型冠状病毒肺炎（COVID-19）感染情况。队列1从2019年新型冠状病毒肺炎大流行开始前起接受欧洲心脏病学会（SCORE）的系统性冠状动脉风险评估。队列2从2017年（新型冠状病毒肺炎大流行前三年）起在医院环境中接受冠状动脉造影，以评估冠状动脉病变情况（以Gensini评分表示）。评估血清中cGAMP和内皮标志物（硝酸盐和亚硝酸盐合并为NOx以及内皮素-1）的水平，通过相关性分析和受试者工作特征分析来评估它们与IgG-SARS状态、SCORE及冠状动脉病变程度之间的关联。
血清cGAMP无法区分队列1中SARS阳性和SARS阴性的健康受试者。此外，健康受试者中cGAMP水平与内皮生物标志物无关。然而，血清cGAMP与动脉粥样硬化相关，曲线下面积为0.69（95%CI 0.587 - 0.806；p = 0.001），并且与队列2中的内皮标志物相关。
低水平cGAMP与冠心病患者动脉粥样硬化相关，提示cGAMP在无菌性炎症背景下是一种新的生物标志物。
