| Autor: |
Sridhar, Arvind, Ly, Olivia T, Arif Pavel, Mahmud, Chen, Hanna, Gonzalez, Francisco, Perike, Srikanth, HONG, Liang, McCauley, Mark, Rehman, Jalees, Darbar, Dawood |
| Zdroj: |
Circulation (Ovid); November 2021, Vol. 144 Issue: Supplement 1 pA11606-A11606, 1p |
| Abstrakt: |
Background:Obesity-induced atrial fibrillation (AF) is modulated in part by increased serum free fatty acids (FFA) and FA infiltration of the heart. Mass spectrometry data on obese mice have shown increased saturated FAs (SFA), monounsaturated FAs (MUFA), and polyunsaturated FAs (PUFA) compared to lean controls with the largest increase in the PUFA, linoleic acid (LA). Although reports suggest that some FAs induce ventricular arrhythmias in mice, the differential electrophysiological (EP) effects of SFAs, MUFAs, and PUFAs on the atria remain unclear.Objective:To determine if SFAs, MUFAs, and PUFAs differentially modulate atrial remodeling using mature human induced pluripotent stem-derived atrial cardiomyocytes (iPSC-aCMs) and HL1 cells. .Methods:We compared iPSC-aCMs and HL-1 cells treated with bovine serum albumin (BSA) with palmitic acid (PA), oleic acid (OA) and LA (600 uM each) for 1 week. Ion channel function was assessed using whole-cell patch clamping and we assessed β-oxidation and atrial remodeling with using ELISA, qPCR, and Western blotting.Results:iPSC-aCMs treated with PA, OA, and LA displayed higher expression of FABP3, ANGPTL4, and CPT1Asuggesting increased FA metabolism and β-oxidation (Figure A-C). In HL1 cells, protein expression of Cpt1a was increased in all groups after FA treatment (Figure D). PA differentially modulated expression of Kv7.1 and NCX1 in HL1 cells (Figure E-F) and ion channel mRNA expression in iPSC-aCMs (Figure G-L). After 1 week PA and LA treatment β-adrenergic signaling was significantly increased in iPSC-aCMs while OA decreased it compared to controls (Figure M-O).Conclusions:Using mature iPSC-aCMs, we showed for the first time that SFA, MUFA, and PUFA not only increased FA metabolism but also differentially modulated ion channel and structural remodeling and β-adrenergic signaling in the atria. Our findings may have important implications for the management of obesity-induced AF in patients. |
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