A novel role of human epicardial adipocyte-derived SPARCL1 in suppression of postoperative atrial fibrillation in patients undergoing cardiovascular surgery

Abstract

Abstract Background Postoperative atrial fibrillation (POAF) occurs in 20-50% after cardiovascular surgery and is closely associated with the short and long-term morbidity/mortality. The epicardial adipose tissue (EAT) is in contact with the atrial muscle, and may have a potential predisposing factor to induce POAF within it. Purpose We tried to identify the specific gene expression profile of the human epicardial adipocyte associated with POAF. Methods We prospectively evaluated 126 patients without a history of AF (male 86 (68.3%); mean age 68.3 ± 11.7) who underwent scheduled open-heart cardiovascular surgery between May 2020 and November 2022. They were assigned to the POAF group and the Non-POAF group. POAF was defined as AF lasting more than 30 seconds documented by monitor or 12-lead electrocardiogram after the operation. Fresh human EAT samples were obtained from these patients during surgery, and preadipocytes were isolated from these samples. Isolated preadipocytes were terminally differentiated to mature adipocytes and RNAs were extracted. Genome-wide expression profiling of 6 vs. 6 matched samples of the POAF and Non-POAF groups was performed using Human Clariom S Assay-HT 16-Array Plate. The secreted protein levels in the adipocytes-cultured medium were also evaluated using enzyme-linked sorbent assay test to confirm the consistency of mRNA expression levels of adipocytes and its secreted protein levels. Results POAF was observed in 48 patients (38%). Patients in the POAF group were significantly older (p = 0.003) compared to the Non-POAF group. POAF occurred mainly within the first 3 postoperative days (median 2.5 days), and the median duration of POAF was 298 ± 581 minutes. The occurrence of POAF was significantly associated with longer postoperative hospitalization (p = 0.001) and intensive care unit stay (p = 0.04). Microarray analysis revealed that there were 132 down- or up-regulated cording genes (fold change >2.0 or `−2.0, p < 0.05) in epicardial adipocytes of the Non-POAF group compared to the POAF group. Of these genes, 11 genes cording secretable molecules were validated by qPCR, showing that only SPARCL1 had significantly higher expression in the Non-POAF group compared to the POAF group (p = 0.008). The mRNA expression levels of SPARCL1 significantly decreased when the preadipocyte were terminally differentiated to the mature adipocyte (p = 0.0009). SPARCL1 mRNA expression in adipocyte was significantly correlated with the concentration of SPARCL1 protein in the adipocyte-cultured medium (p < 0.0001, r = 0.7476). Conclusion The results of this study suggest that the expression of SPARCL1 in human epicardial adipocytes may play an important role in the suppression of POAF. Our findings suggested that SPARCL1 expression in human epicardial adipocytes may play an important role in the suppression of POAF. SPARCL1 secreted by epicardial adipocytes may be a potential therapeutic target for POAF prevention.Flowchart of patient selectionMicroarray analysis and qPCR varidation