Endothelial‐to‐mesenchymal transition (EndMT) was first reported in heart development. Recent studies have shown that EndMT also occurs in the progression of cardiac fibrosis. Herein, we demonstrated a critical role of the Forkhead Box M1 (Foxm1) transcription factor in transforming growth factor beta (TGF‐β)‐induced EndMT in endothelial cells (ECs) and a possible underlying molecular mechanism. Foxm1 was induced in ECs following TGF‐β stimulation. Using both pharmacological and molecular approaches to inhibit Foxm1 function can attenuate the TGF‐β‐induced EndMT and cell migration. In contrast, lentivirus‐mediated overexpression of Foxm1 allowed EndMT to proceed despite the absence of TGF‐β in ECs. Moreover, we found that the activation of the Smad2/3 signaling pathway and EndMT‐related transcription factors played important roles in the pathogenesis of Foxm1‐mediated EndMT. Further analysis revealed that Foxm1 bound to and increased the promoter activity of the Snail gene encoding a critical transcriptional regulator of EndMT. In conclusion, our results identify FOXM1 as a driver of TGF‐β‐induced EndMT and underscore the therapeutic potential of targeting FOXM1 for cardiac fibrosis.

Atrial cardiomyopathy (ACM) is responsible for atrial fibrillation (AF) and thromboembolic events. Diabetes mellitus (DM) is an important risk factor for ACM. However, the potential mechanism between ACM and DM remains elusive. Atrial tissue samples were obtained from patients diagnosed with AF or sinus rhythm (SR) to assess alterations in NR4A3 expression, and then two distinct animal models were generated by subjecting Nr4a3-/- mice and WT mice to a high-fat diet (HFD) and Streptozotocin (STZ), while db/db mice were administered AAV9-Nr4a3 or AAV9-ctrl. Subsequently, in vivo and in vitro experiments were conducted to assess the impact of NR4A3 on diabetes-induced atrial remodeling through electrophysiological, biological, and histological analyses. RNA sequencing (RNA-seq) and metabolomics analysis were employed to unravel the downstream mechanisms. The expression of NR4A3 was significantly decreased in atrial tissues of both AF patients and diabetic mice compared to their respective control groups. NR4A3 deficiency exacerbated atrial hypertrophy and atrial fibrosis, and increased susceptibility to pacing-induced AF. Conversely, overexpression of NR4A3 alleviated atrial structural remodeling and reduced AF induction rate. Mechanistically, we confirmed that NR4A3 improves mitochondrial energy metabolism and reduces oxidative stress injury by preserving the transcriptional expression of Sdha, thereby exerting a protective influence on atrial remodeling induced by diabetes. Our data confirm that NR4A3 plays a protective role in atrial remodeling caused by diabetes, so it may be a new target for treating ACM. This study was supported by the major research program of National Natural Science Foundation of China (NSFC) No: 82370316 (to Q-S. W.), No. 81974041 (to Y-P. W.), and No. 82270447 (to Y-P. W.) and Fundation of Shanghai Hospital Development Center (No. SHDC2022CRD044 to Q-S. W.).

Enhancer of zeste homolog 2(EZH2) is an enzymatic subunit of polycomb repressive complex 2 (PRC2) and is responsible for catalyzing mono-, di-, and trimethylation of histone H3 at lysine-27(H3K27me1/2/3). Many noncoding RNAs or signaling pathways are involved in EZH2 functional alterations. This new epigenetic regulation of target genes is able to silence downstream gene expression and modify physiological and pathological processes in heart development, cardiomyocyte regeneration, and cardiovascular diseases, such as hypertrophy, ischemic heart diseases, atherosclerosis, and cardiac fibrosis. Targeting the function of EZH2 could be a potential therapeutic approach for cardiovascular diseases.

Aims : We evaluated the feasibility of left atrial appendage (LAA) closure guided by the image fusion of integrating fluoroscopy into 3D computed tomography (CT). Methods and results : A total of 117 consecutive patients who underwent LAA closure with or without the image fusion were matched (1:2). Each LAA closure step of the Image fusion group was guided by the preprocedure CT and image fusion, especially in the plan of LAA measurement and transseptal puncture. All patients were successfully implanted with a WATCHMAN closure device. Comparing the two groups, the mean number of recapture times and the number of devices per patient of the Image fusion group were significantly lower (0.4 ± 0.5 vs. 0.7 ± 0.8, P = 0.031 and 1.0 ± 0.2 vs. 1.1 ± 0.3, P = 0.027, respectively). The one-time successful deployment rate by the support of the image fusion was higher than in the control group (66.7% vs. 44.9%, P = 0.026). Each case of the Image fusion group was completely occluded with one transseptal puncture, while five of the Non-image fusion group required redo transseptal punctures. During the 45-day follow-up, both group cases presented occlusion efficiency and no major adverse cardiac events were observed. Conclusion : Image fusion technique integrating fluoroscopy into the 3D CT is safe and feasible which can be easily incorporated into the procedural work-flow of percutaneous LAA closure. The fusion image can play an important alternative role in the plan of LAA measurement and transseptal puncture site for improving the LAA closure procedure.