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Background: A close association exists between renal impairment (RI) and atrial fibrillation (AF) occurrence. Increased activity of the sympathetic nervous system (SNS) may contribute to the development of AF associated with RI. Renal denervation (RDN) decreases central sympathetic activity. Objective: The main objective of the study was to explore the effects of RDN on AF occurrence and its possible mechanisms in beagles with RI. Methods: Unilateral RI was induced in beagles by embolization of small branches of the renal artery in the right kidney using gelatin sponge granules in Model (n = 6) and RDN group (n = 6). The Sham group (n = 6) underwent the same procedure, except for embolization. Then animals in RDN group underwent radiofrequency ablation of the renal sympathetic nerve. Cardiac electrophysiological parameters, blood pressure, left ventricular end-diastolic pressure, and AF inducibility were investigated. The activity of the SNS, renin-angiotensin-aldosterone system (RAAS), inflammation and atrial interstitial fibrosis were measured. Results: Embolization of small branches of the renal artery in the right kidney led to ischemic RI. Heart rate, P wave duration and BP were increased by RI, which were prevented or attenuated by RDN. Atrial effective refractory period was shortened and AF inducibility was increased by RI, which were prevented by RDN. Antegrade Wenckebach point was shortened, atrial and ventricular rates during AF were increased by RI, which were attenuated or prevented by RDN. Levels of norepinephrine, renin and aldosterone in plasma, norepinephrine, angiotensin II, aldosterone, interleukin-6 and high sensitivity C-reactive protein in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced by RI, which were attenuated by RDN. Conclusions: RDN significantly reduced AF inducibility, prevented the atrial electrophysiological changes in a model of RI by combined reduction of sympathetic drive and RAAS activity, and inhibition of inflammation activity and fibrotic pathway in atrial tissue. [ABSTRACT FROM AUTHOR]

[Display omitted] • Unveiled common DEGs in EAT linking T2DM and AF, spotlighting metabolic and immune dysregulation. • Employed bioinformatics and db/db mouse models to validate hub genes' roles in T2DM and AF crosstalk. • Revealed CEBPZ, PAK1IP1, and BCCIP as central regulators in EAT, influencing T2DM and AF pathology. • Regulatory networks of miRNAs and TFs related to hub genes deepen understanding of T2DM and AF interplay. The complex relationship between atrial fibrillation (AF) and type 2 diabetes mellitus (T2DM) suggests a potential role for epicardial adipose tissue (EAT) that requires further investigation. This study employs bioinformatics and experimental approaches to clarify EAT's role in linking T2DM and AF, aiming to unravel the biological mechanisms involved. Bioinformatics analysis initially identified common differentially expressed genes (DEGs) in EAT from T2DM and AF datasets. Pathway enrichment and network analyses were then performed to determine the biological significance and network connections of these DEGs. Hub genes were identified through six CytoHubba algorithms and subsequently validated biologically, with further in-depth analyses confirming their roles and interactions. Experimentally, db/db mice were utilized to establish a T2DM model. AF induction was executed via programmed transesophageal electrical stimulation and burst pacing, focusing on comparing the incidence and duration of AF. Frozen sections and Hematoxylin and Eosin (H&E) staining illuminated the structures of the heart and EAT. Moreover, quantitative PCR (qPCR) measured the expression of hub genes. The study identified 106 DEGs in EAT from T2DM and AF datasets, underscoring significant pathways in energy metabolism and immune regulation. Three hub genes, CEBPZ, PAK1IP1, and BCCIP, emerged as pivotal in this context. In db/db mice, a marked predisposition towards AF induction and extended duration was observed, with HE staining verifying the presence of EAT. Additionally, qPCR validated significant changes in hub genes expression in db/db mice EAT. In-depth analysis identified 299 miRNAs and 33 TFs as potential regulators, notably GRHL1 and MYC. GeneMANIA analysis highlighted the hub genes' critical roles in stress responses and leukocyte differentiation, while immune profile correlations highlighted their impact on mast cells and neutrophils, emphasizing the genes' significant influence on immune regulation within the context of T2DM and AF. This investigation reveals the molecular links between T2DM and AF with a focus on EAT. Targeting these pathways, especially EAT-related ones, may enable personalized treatments and improved outcomes. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease and occurrence of atrial fibrillation (AF) are closely related. No studies have examined whether renal impairment (RI) without severe renal dysfunction is associated with the occurrence of AF. Methods: Unilateral RI with mild renal insufficiency was induced in beagles by embolization of small branches of the renal artery in the left kidney for 2 weeks using gelatin sponge granules in the model group (n = 5). The sham group (n = 5) underwent the same procedure, except for embolization. Parameters associated with RI and renal function were tested, cardiac electrophysiological parameters, blood pressure, left ventricular pressure, and AF vulnerability were investigated. The activity of the sympathetic nervous system, renin-angiotensin-aldosterone system, inflammation, and oxidative stress were measured. Histological studies associated with atrial interstitial fibrosis were performed. Results: Embolization of small branches of the renal artery in the left kidney led to ischemic RI with mild renal insufficiency. The following changes occurred after embolization. Heart rate and P wave duration were increased. Blood pressure and left ventricular systolic pressure were elevated. The atrial effective refractory period and antegrade Wenckebach point were shortened. Episodes and duration of AF, as well as atrial and ventricular rate during AF were increased in the model group. Plasma levels of norepinephrine, renin, and aldosterone were increased, angiotensin II and aldosterone levels in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced after 2 weeks of embolization in the model group. Conclusions: We successfully established a model of RI with mild renal insufficiency in a large animal. We found that RI with mild renal insufficiency was associated with AF in this model. [ABSTRACT FROM AUTHOR]