Divergent Atrial Transcriptomic Signatures in Diabetic and Nondiabetic Atrial Fibrillation

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Genomics

Background:

• Diabetes mellitus (DM) is a known risk factor for atrial fibrillation (AF).
• The precise molecular mechanisms driving DM-associated atrial remodeling are not fully understood.
• Investigating transcriptomic and microRNA differences in atrial tissue from AF patients with and without DM is crucial.

Purpose of the Study:

• To characterize the transcriptomic and microRNA profiles of atrial tissue in patients with atrial fibrillation (AF) and diabetes mellitus (DM).
• To identify molecular pathways and epigenetic regulators involved in DM-related atrial remodeling.
• To elucidate the mechanisms underlying the increased risk of AF in diabetic individuals.

Main Methods:

• Analysis of right atrial appendage tissue from 12 AF patients (6 with DM, 6 without DM).
• High-throughput RNA sequencing to identify differentially expressed genes (DEGs) and microRNAs (miRNAs).
• Pathway analysis using Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA).

Main Results:

• Identification of 46 DEGs and 9 differentially expressed miRNAs between the groups.
• Upregulated genes (e.g., MYH6, SLN) associated with contractile and calcium handling; downregulated genes (e.g., ADAMTS4, CP) linked to extracellular matrix and chromatin.
• Pathway analysis indicated activation of mitochondrial ATP synthesis and suppression of immune/inflammatory signaling, alongside distinct miRNA expression changes (e.g., miR-3120, miR-4524B, miR-6503).

Conclusions:

• Atrial fibrillation in diabetic patients exhibits distinct transcriptomic signatures characterized by heightened mitochondrial metabolism and reduced immune responses.
• Diabetes mellitus appears to induce atrial substrate modifications via metabolic and epigenetic pathways.
• These findings provide novel insights into the pathogenesis of AF in the context of diabetes.