PO-02-124 MITOCHONDRIAL GLYCEROL-3-PHOSPHATE DEHYDROGENASE ACTS AT THE CROSSROAD OF METABOLISM REPROGRAMMING IN NON-VALVULAR ATRIAL FIBRILLATION: INDICATION FROM MULTI-OMICS ANALYSIS OF HUMAN AF MYOCARDIAL TISSUE

Metabolic remodeling has been known to play an important role in the development of atrial fibrillation(AF). Recent studies have shown prominent mitochondrial metabolic changes atrium, which significant impact on electrical signaling and structural atrium. However, there is limited data AF from multi-omics analysis human myocardial tissue. In addition, metabolism-related hub gene pathways are not completely known. We aimed explore metabolism reprogrammed AF, describe key dysregulated molecules patients, as well related pathways. In-hospital patients diagnosed with 2019 2022 were enrolled. Left appendages harvested undergoing cardiovascular surgery matched ones healthy donors sinus rhythm(SR). Metabolomics proteomics then performed analyzed. Moreover, biostatistical was done for further identification. Heart tissue samples 10 persistent non-valvular (Table1) SR donors. metabolomics analysis, 113 metabolites up-regulated down-regulated (Panel A), where multiple amino acid glycolipid enriched B). After correlation between differentially expressed proteins metabolites, glycerol-3-phosphate dehydrogenase (mGPDH) found crucial both positive- negative-ionized mode (MCC score=16 MCC score=6 respectively)(Panel C-D), locates inner membrane mitochondria participates cardiac function glucolipid homeostasis. Proteomics revealed that demonstrated marked difference hearts than SR, especially oxidative phosphorylation (NES=-1.73)(Panel E), ATP biosynthetic process (NES:-2.29), NADH (NES:-2.36) etc., closely mGPDH. The expression level mGPDH associated using set variation validated by external database F). Mitochondrial underwent reprogramming AF. may participate via regulating contribute remodeling, could be considered a novel target treatment.