Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Biomolecules. 2022 Aug 15;12(8):1120. doi: 10.3390/biom12081120.
Phenylacetylglutamine (PAGln), a gut microbiota (GM)-derived metabolite, is associated with cardiovascular disease. Studies have shown that disordered GM participated in the progression of atrial fibrillation (AF), but the relationship between PAGln and AF is unclear. This study investigated the characteristics of PAGln in AF patients and its impact on atrial myocytes. Based on our previous metagenomic data, the relative abundance of porA, a critical bacterial enzyme for PAGln synthesis, exhibited an increased tendency in AF. In an independent cohort consisting of 42 controls without AF and 92 AF patients, plasma PAGln levels were higher in AF patients than in controls (p < 0.001) by immunoassay. Notably, PAGln exerted a predictive potential of AF with an AUC of 0.774 (p < 0.001), and a predictive model constructed based on the PAGln and Taiwan AF score further improved the predictive potential. Furthermore, a positive correlation was determined between PAGln and LA diameter. Subsequently, the effect of PAGln intervention was examined on HL-1 cells in vitro, revealing that PAGln increased apoptosis, reactive oxygen species (ROS) production, CaMKII and RyR2 activation and decreased cell viability. In conclusion, increased PAGln was associated with AF, and PAGln might contribute to the AF pathogenesis by promoting oxidative stress and apoptosis in atrial myocytes.
苯乙酰谷氨酰胺（PAGln）是一种肠道微生物群（GM）衍生的代谢物，与心血管疾病有关。研究表明，GM 紊乱参与了心房颤动（AF）的进展，但 PAGln 与 AF 的关系尚不清楚。本研究调查了 PAGln 在 AF 患者中的特征及其对心房肌细胞的影响。基于我们之前的宏基因组数据，PAGln 合成的关键细菌酶 porA 的相对丰度在 AF 中表现出增加的趋势。在一个由 42 名无 AF 的对照者和 92 名 AF 患者组成的独立队列中，通过免疫测定发现 AF 患者的血浆 PAGln 水平高于对照者（p<0.001）。值得注意的是，PAGln 对 AF 的预测潜力具有 AUC 为 0.774（p<0.001）的预测能力，并且基于 PAGln 和台湾 AF 评分构建的预测模型进一步提高了预测潜力。此外，还确定了 PAGln 与 LA 直径之间存在正相关关系。随后，在体外 HL-1 细胞上检查了 PAGln 干预的效果，结果表明 PAGln 增加了细胞凋亡、活性氧（ROS）产生、CaMKII 和 RyR2 的激活，并降低了细胞活力。总之，PAGln 的增加与 AF 有关，PAGln 可能通过促进心房肌细胞中的氧化应激和细胞凋亡来促进 AF 的发病机制。
