Single-nucleus RNA sequencing of epicardial adipose tissue revealed extensive remodeling in atrial fibrillation including impaired neuroprotective programs, metabolic imbalance, profibrotic activation, and chronic inflammatory milieu, with elevated plasma interleukin-17 identified as a predictive biomarker for AF.
Higher visceral adipose tissue was associated with increased atrial fibrillation risk in the National Health and Nutrition Examination Survey (NHANES) population.
Mendelian randomization provided genetic evidence consistent with a potential causal contribution of visceral adipose tissue to atrial fibrillation.
Single-nucleus RNA sequencing revealed extensive epicardial adipose tissue remodeling in patients with coronary artery disease and atrial fibrillation compared to those without AF.
Impaired neuroprotective and myelin-maintenance programs were identified as features of EAT remodeling in AF.
A chronic inflammatory milieu with immunoglobulin G-related humoral immune activation was identified in AF-associated EAT.
Drug2cell analysis prioritized candidate drug-cell associations across specific EAT cell populations in AF.
Summary data-based Mendelian randomization prioritized PTPRN2 as a putative AF susceptibility gene.
Higher plasma interleukin-17 levels were associated with postoperative atrial fibrillation in the Fuwai Hospital cohort.
Circulating interleukin-17C and interleukin-17D were independently associated with incident atrial fibrillation in the UK Biobank.
Elevated plasma interleukin-17 may serve as a predictive biomarker for atrial fibrillation.
This research suggests that the fat tissue surrounding the heart, called epicardial adipose tissue (EAT), undergoes profound changes in patients with atrial fibrillation (AF), the most common sustained irregular heart rhythm. Using a powerful technique called single-nucleus RNA sequencing, researchers mapped the molecular activity of individual cells in EAT from patients who had both coronary artery disease and AF, compared to patients with coronary artery disease alone. They found that AF-associated EAT showed signs of nerve damage, disrupted energy metabolism, scar-forming activity, and chronic immune system activation — including unusual antibody-related immune responses. The study also used large population databases and genetic analysis approaches (Mendelian randomization) to support the idea that having more visceral (internal belly) fat may causally contribute to AF risk, not just be associated with it. A key translational finding was that a family of inflammatory signaling proteins called interleukin-17 (IL-17) appears to be elevated in AF patients across two independent clinical cohorts. Higher IL-17 levels predicted AF developing after heart surgery in patients at Fuwai Hospital, and higher levels of specific IL-17 variants (IL-17C and IL-17D) were independently linked to new-onset AF in the large UK Biobank population study. The researchers also used computational tools to identify existing drugs that might target the specific cell types found to be abnormal in AF-related EAT, and identified a gene called PTPRN2 as a possible genetic risk factor for AF through multiomics analysis. This research suggests that the fat around the heart is not merely a passive bystander in AF but plays an active role through multiple pathways including nerve damage, metabolic dysfunction, scarring, and inflammation. The identification of IL-17 as a potential blood biomarker for AF risk could eventually help clinicians identify patients at higher risk before they develop the condition. Additionally, the comprehensive cellular map of AF-related EAT created in this study may serve as a resource for future research into new drug targets for AF prevention or treatment.
Huang S, Yang Z, Zhong X, Li C, Zhen J, Cai X, et al.. (2026). Single-Nucleus and Multiomics Profiling of Epicardial Adipose Tissue in Atrial Fibrillation Reveals Novel Mechanisms and Translational Biomarkers.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.126.049221