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Atrial fibrillation (AF) is the most common arrhythmia, and atrial fibrosis is a pathological hallmark of structural remodeling in AF. Prostaglandin I2 (PGI2) can prevent the process of fibrosis in various tissues via cell surface Prostaglandin I2 receptor (IP). However, the role of PGI2 in AF and atrial fibrosis remains unclear. The present study aimed to clarify the role of PGI2 in angiotensin II (Ang II)-induced AF and the underlying molecular mechanism. PGI2 content was decreased in both plasma and atrial tissue from patients with AF and mice treated with Ang II. Treatment with the PGI2 analog, iloprost, reduced Ang II-induced AF and atrial fibrosis. Iloprost prevented Ang II-induced atrial fibroblast collagen synthesis and differentiation. RNA-sequencing analysis revealed that iloprost significantly attenuated transcriptome changes in Ang II-treated atrial fibroblasts, especially mitogen-activated protein kinase (MAPK)-regulated genes. We demonstrated that iloprost elevated cAMP levels and then activated protein kinase A, resulting in a suppression of extracellular signal-regulated kinase1/2 and P38 activation, and ultimately inhibiting MAPK-dependent interleukin-6 transcription. In contrast, cardiac fibroblast-specific IP-knockdown mice had increased Ang II-induced AF inducibility and aggravated atrial fibrosis. Together, our study suggests that PGI2/IP system protects against atrial fibrosis and that PGI2 is a therapeutic target for treating AF. The prospectively registered trial was approved by the Chinese Clinical Trial Registry. The trial registration number is ChiCTR2200056733. Data of registration was 2022/02/12. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) is a leading cause of mortality in patients with end-stage renal disease (ESRD) undergoing haemodialysis. Identifying novel predictors of HF is essential for improving diagnostic precision and enhancing patient outcomes., Methods: This study included 68 participants from the Haemodialysis Centre at the Second Hospital of Tianjin Medical University. Clinical characteristics and echocardiographic data were collected and analysed. We measured the plasma of 44 cytokines to investigate their correlation with cardiac function and their potential as HF biomarkers., Results: In the HF with reduced ejection fraction (HFrEF) group, the levels of several cytokines, including stem cell growth factor-β (SCGF-β), C-X-C motif chemokine 10 (CXCL10), interleukin-1α (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-16 (IL-16), interleukin-1 receptor antagonist protein (IL-1Ra), interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), leukaemia inhibitory factor (LIF), C-C motif chemokine 3 (CCL3), interleukin-10 (IL-10), interleukin-2 receptor subunit alpha (IL-2Rα), tumour necrosis factor ligand superfamily member 10 (TNFSF10), macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF), were significantly increased, while C-C motif chemokine 11 (CCL11)/eotaxin levels were decreased compared with those in the control group (P < 0.05). Receiver operating characteristic (ROC) curve analysis highlighted TNF-α [area under the ROC curve (AUC) = 0.85, odds ratio (OR) = 1.080, 95% confidence interval (CI): 1.033-1.128, P = 0.001], IFN-γ (AUC = 0.84, OR = 1.836, 95% CI: 1.289-2.615, P = 0.003) and IL-2Rα (AUC = 0.82, OR = 1.022, 95% CI: 1.009-1.035, P = 0.001) as excellent predictors for HFrEF in haemodialysis patients with ESRD, and they outperformed soluble suppression of tumourigenicity-2 (sST2) but slightly underperformed N-terminal pro-brain natriuretic peptide (NT-proBNP). IL-2Rα (AUC = 0.77, OR = 1.018, 95% CI: 1.007-1.030, P = 0.001) demonstrated superior diagnostic capabilities when distinguishing patients with HF with left ventricular ejection fraction (LVEF) <50% from controls. IL-2Rα emerged as a robust biomarker for left ventricular HF, while TNF-α (AUC = 0.89, OR = 1.140, 95% CI: 1.039-1.250, P = 0.005) showed promise in assessing HF severity in patients with ESRD. IL-2Rα (AUC = 0.80, OR = 1.017, 95% CI: 1.007-1.027, P = 0.001) also significantly predicted right ventricular systolic dysfunction. During a median follow-up of 14 months, 10 patients (14.7%) experienced all-cause mortality. Multivariate Cox regression analysis confirmed that plasma IL-2Rα was an independent predictor of all-cause death [hazard ratio (HR): 1.010, 95% CI: 1.001-1.020, P = 0.039] after adjusting for other variables., Conclusions: This study underscores the potential of IL-2Rα as a valuable biomarker for HF diagnosis and management in haemodialysis patients with ESRD and contributes to our understanding of this high-risk population., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Atrial fibrillation (AF) is the most common arrhythmia, and atrial fibrosis is a pathological hallmark of structural remodeling in AF. Prostaglandin I 2 (PGI 2 ) can prevent the process of fibrosis in various tissues via cell surface Prostaglandin I 2 receptor (IP). However, the role of PGI 2 in AF and atrial fibrosis remains unclear. The present study aimed to clarify the role of PGI 2 in angiotensin II (Ang II)-induced AF and the underlying molecular mechanism. PGI 2 content was decreased in both plasma and atrial tissue from patients with AF and mice treated with Ang II. Treatment with the PGI 2 analog, iloprost, reduced Ang II-induced AF and atrial fibrosis. Iloprost prevented Ang II-induced atrial fibroblast collagen synthesis and differentiation. RNA-sequencing analysis revealed that iloprost significantly attenuated transcriptome changes in Ang II-treated atrial fibroblasts, especially mitogen-activated protein kinase (MAPK)-regulated genes. We demonstrated that iloprost elevated cAMP levels and then activated protein kinase A, resulting in a suppression of extracellular signal-regulated kinase1/2 and P38 activation, and ultimately inhibiting MAPK-dependent interleukin-6 transcription. In contrast, cardiac fibroblast-specific IP-knockdown mice had increased Ang II-induced AF inducibility and aggravated atrial fibrosis. Together, our study suggests that PGI 2 /IP system protects against atrial fibrosis and that PGI 2 is a therapeutic target for treating AF.The prospectively registered trial was approved by the Chinese Clinical Trial Registry. The trial registration number is ChiCTR2200056733. Data of registration was 2022/02/12., (© 2024. The Author(s).)