Novel Role of Human Epicardial Adipocyte-Derived SPARCL1 in Postoperative Atrial Fibrillation Following Cardiovascular Surgery

Abstract

Background: Postoperative atrial fibrillation (POAF) is associated with short- and long-term morbidity and mortality. However, the ability of the epicardial adipocyte to regulate POAF remains poorly understood.

Objectives: The authors investigated the possible role of human epicardial adipocyte-derived adipokines in the regulation of the myocardial redox state and POAF.

Methods: The authors prospectively studied 274 patients who underwent scheduled open-heart surgery. Finally, 149 patients without known atrial fibrillation were enrolled and divided into POAF and non-POAF groups. Epicardial adipose tissue biopsies and isolated preadipocytes were used to explore the important secretable adipokines associated with POAF.

Results: POAF occurred in 53 (35.6%) patients. Genome-wide expression profiling of background-matched differentiated preadipocytes representing the POAF or non-POAF groups and quantitative polymerase chain reaction validation as a biological replicate using all cohort samples revealed that only SPARCL1 was significantly downregulated in the POAF group. SPARCL1 messenger RNA expression in differentiated preadipocytes correlated with SPARCL1 protein concentration in the preadipocyte culture medium. SPARCL1 attenuated angiotensin II-induced oxidative stress in neonatal rat myocytes. Coculture of human induced pluripotent stem cell-derived atrial cardiomyocyte with the differentiated preadipocyte revealed that the preadipocytes derived from non-POAF patients suppressed myocardial oxidative stress. Low SPARCL1 expression in human epicardial differentiated preadipocytes was associated with a higher risk of long-term adverse cardiovascular events after surgery.

Conclusions: These findings suggested that the SPARCL1, derived from epicardial differentiated preadipocytes, may be an important paracrine adipokine that regulates POAF and subsequent cardiovascular outcomes by improving myocardial redox state.

Keywords: adipokine; epicardial adipose tissue; epicardial differentiated preadipocyte; myocardial redox state; postoperative atrial fibrillation.