冠状窦代谢产物 12,13-二氢二十碳四烯酸是心房颤动患者左心房重构的新型生物标志物。

Coronary Sinus Metabolite 12,13-diHOME Is a Novel Biomarker for Left Atrial Remodeling in Patients With Atrial Fibrillation.

机构信息

VIP Medical Service Center (X.T.), the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Department of Cardiovascular Medicine (J.W., X.O., Q.C., R.D., Y.L., Z.H., L.P., X.X., J.Z., Z.Z., S.L.), the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

Circ Arrhythm Electrophysiol. 2024 Jun;17(6):e012486. doi: 10.1161/CIRCEP.123.012486. Epub 2024 May 1.

DOI:10.1161/CIRCEP.123.012486

PMID:38690652

Abstract

BACKGROUND

12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) has shown potential in protecting against heart disease, but its relationship with atrial fibrillation (AF) remains unknown.

METHODS

Coronary sinus (CS) and femoral vein blood samplings were synchronously collected from AF and non-AF subjects (paroxysmal supraventricular tachycardia or idiopathic premature ventricular complexes) who underwent catheter ablation. First, untargeted metabolomic profiling was performed in a discovery cohort (including 12 AF and 12 non-AF subjects) to identify the most promising CS or femoral vein metabolite. Then, the selected metabolite was further measured in a validation cohort (including 119 AF and 103 non-AF subjects) to confirm its relationship with left atrium remodeling and 1-year postablation recurrence of AF. Finally, the biological function of the selected metabolite was validated in a rapid-paced cultured HL-1 atrial cardiomyocytes model.

RESULTS

Metabolomic analysis identified CS 12,13-diHOME as the most pronounced change metabolite correlated with left atrium remodeling in the discovery cohort. In the validation cohort, CS 12,13-diHOME was significantly lower in patients with AF than non-AF controls (84.32±20.13 versus 96.24±23.56 pg/mL; <0.01), and associated with worse structural, functional, and electrical remodeling of left atrium. Multivariable regression analyses further demonstrated that decreased CS 12,13-diHOME was an independent predictor of 1-year postablation recurrence of AF (odds ratio, 0.754 [95% CI, 0.648-0.920]; =0.005). Biological function validations showed that 12,13-diHOME treatment significantly protect the cell viability, improved the expression of MHC (myosin heavy chain) and Cav1.2 (L-type calcium channel α1c), and attenuated mitochondrial damage in the rapid-paced cultured HL-1 cardiomyocytes model.

CONCLUSIONS

CS metabolite 12,13-diHOME is decreased in patients with AF and can serve as a novel biomarker for left atrium remodeling.

摘要

背景

12,13-二羟基-9Z-十八碳烯酸（12,13-二 HOME）在预防心脏病方面显示出潜力，但它与心房颤动（AF）的关系尚不清楚。

方法

从接受导管消融的 AF 和非 AF 患者（阵发性室上性心动过速或特发性室性早搏）同步采集冠状窦（CS）和股静脉血样。首先，在发现队列（包括 12 例 AF 和 12 例非 AF 患者）中进行非靶向代谢组学分析，以确定最有前途的 CS 或股静脉代谢物。然后，在验证队列（包括 119 例 AF 和 103 例非 AF 患者）中进一步测量所选代谢物，以确认其与左心房重构和消融后 1 年 AF 复发的关系。最后，在快速起搏培养的 HL-1 心房肌细胞模型中验证所选代谢物的生物学功能。

结果

代谢组学分析确定 CS 12,13-二 HOME 是发现队列中与左心房重构相关性最强的明显变化代谢物。在验证队列中，AF 患者 CS 12,13-二 HOME 明显低于非 AF 对照组（84.32±20.13 与 96.24±23.56 pg/mL；<0.01），与左心房结构、功能和电重构恶化相关。多变量回归分析进一步表明，CS 12,13-二 HOME 降低是消融后 1 年 AF 复发的独立预测因子（比值比，0.754 [95%CI，0.648-0.920]；=0.005）。生物学功能验证表明，12,13-二 HOME 治疗可显著保护细胞活力，提高 MHC（肌球蛋白重链）和 Cav1.2（L 型钙通道α1c）的表达，并减轻快速起搏培养的 HL-1 心肌细胞模型中的线粒体损伤。