Identification of mitochondria-associated endoplasmic reticulum membranes-related biomarkers for atrial fibrillation

Aims: To provide novel insights into the diagnosis of atrial fibrillation (AF), we aimed to identify mitochondria-associated endoplasmic reticulum membranes (MAMs)-related biomarkers for AF.

Methods: A comprehensive analysis was conducted to identify MAM-related biomarkers, including machine learning algorithms and expression analysis. Moreover, causal effects of biomarkers on AF were assessed through the two-sample mendelian randomization (MR) analysis. Subsequently, functional enrichment, immune infiltration, and single-cell studies were performed to explore the potential mechanisms by which biomarkers regulate AF. Finally, the expression of biomarkers was validated at the protein level by developing an in-vivo AF model.

Results: Through the comprehensive analysis, TP53, HLA-G, and MAPKAPK5 were identified as biomarkers for AF, and these genes were highly expressed in AF. Among these genes, MAPKAPK5 was a risk factor for occurrence of AF (P = 0.022, OR = 1.065, 95%CI = 1.009-1.125). Enrichment analysis indicated that three biomarkers were linked to immune-related pathways. Immune infiltration further demonstrated that a total of infiltration abundance of 18 immune cells was significantly different between AF and controls, and all biomarkers had marked positive associations with these immune cells. Moreover, at the cellular level, the expression of TP53 and MAPKAPK5 was markedly different in lymphoid cells and neutrophils between AF and controls. The protein expression of three indicators was markedly elevated in the AF model compared to the control model, aligning with the bioinformatics findings.

Conclusions: We identified three potential MAMs-related biomarkers (TP53, HLA-G, and MAPKAPK5) for AF, thereby providing novel insights for the prevention and treatment of AF.

Dr. Wang is a scholar in the fields of cardiometabolic and arrhythmia research, holding a master's degree and a Ph.D. in clinical medicine from Wuhan University. Dr. Liu holds a master's degree in public health from Guangdong Medical University, and she is currently working as a research assistant at the Dongguan Cardiovascular Disease Research Institute. Prof. Yan primarily engages in research related to cardiovascular aging and has published a significant number of research findings in this field. He is currently the director of the Dongguan Cardiovascular Disease Research Institute.