Bo Dong

Circular noncoding RNAs (circRNAs) are implicated in many human diseases, but their role in atrial fibrillation (AF) is poorly understood. In this study, we performed bioinformatics analysis of circRNA sequencing data to identify AF-related circRNAs. Left atrial appendage (LAA) samples were obtained from patients with valvular heart disease and were categorised into the sinus rhythm (SR; n = 4) and AF (n = 4) groups. CircRNA sequencing analysis was performed to identify differentially expressed (DE) circRNAs in AF patients. Functional enrichment analysis of DE circRNAs was performed to identify enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. We identified 3338 DE circRNAs, including 2147 upregulated and 1191 downregulated circRNAs, in AF patients. A ceRNA network of 16 DE circRNAs, 11 DE miRNAs, and 15 DE mRNAs was constructed. Functional enrichment analyses revealed that the AF-related DE circRNAs were enriched in response to vitamin D, the potassium channel complex, delayed rectifier potassium channel activity, osteoclast differentiation, primary immunodeficiency, endocrine and other factor-regulated calcium reabsorption and other processes. ROC curve analysis identified circRNA_00324, circRNA_17225, circRNA_16305, circRNA_10233, circRNA_05499, circRNA_03183, circRNA_14211, and circRNA_18422 as potential predictive biomarkers for distinguishing AF patients from SR patients, with AUC values of 0.9138, 0.7370, 0.8526, 0.6803, 0.8163, 0.8662, 0.7664, and 0.9320, respectively. In this study, we constructed an AF-related ceRNA network and identified eight circRNAs as potential predictive biomarkers of AF.

Sustained production of reactive oxygen species (ROS) and an imbalance in the antioxidant system have been implicated in the development of cardiovascular diseases (CVD), especially when combined with diabetes, hypercholesterolemia, and other metabolic disorders. Among them, NADPH oxidases (NOX), including NOX1-5, are major sources of ROS that mediate redox signaling in both physiological and pathological processes, including fibrosis, hypertrophy, and remodeling. Recent studies have demonstrated that mitochondria produce more proteins and energy in response to adverse stress, corresponding with an increase in superoxide radical anions. Novel NOX4-mediated modulatory mechanisms are considered crucial for maintaining energy metabolism homeostasis during pathological states. In this review, we integrate the latest data to elaborate on the interactions between oxidative stress and energy metabolism in various CVD, aiming to elucidate the higher incidence of CVD in individuals with metabolic disorders. Furthermore, the correlations between NOX and ferroptosis, based on energy metabolism, are preliminarily discussed. Further discoveries of these mechanisms might promote the development of novel therapeutic drugs targeting NOX and their crosstalk with energy metabolism, potentially offering efficient management strategies for CVD.

Error in Figure/TableIn the published article, there was an error in Figure 7G and 7J as published. We lacked the analysis diagram for LVEF and repeatedly inserted the wrong E/A analysis diagram in this figure 7G and 7J. The corrected Figure 7G and 7J and its caption ** (G) Quantitative analysis of LVEF in rats; (J) Quantitative analysis of E/A ratio in rats appear below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

Downregulated in Metastasis Protein (DRIM) was discovered in malignant epithelial cells and was thought to be mainly a nucleus protein affecting cancer cells. Recent single‐cell sequencing analysis suggests that DRIM is abundantly expressed in vascular endothelial cells. There has been no knowledge of the role of DRIM in the endothelium. In the present study, using protein fraction method and cell imaging, we identified that the DRIM protein was abundantly present in both nucleus and the cytoskeletal fractions of human vascular endothelial cells. Knockdown of DRIM in the endothelial cells significantly affected growth, migration, and angiogenic tubule formation. Proteomics analyses revealed that Src was an important direct target protein of DRIM, a finding further confirmed by protein interaction assay. Silencing DRIM activated the tyrosine 419 site phosphorylation of Src kinase in endothelial cells, thereby affecting the downstream proteins of Src including p‐FAK and p‐STAT3, and exerting biological effects. To conclude, our results provide evidence of DRIM being a nuclear and cytoskeletal‐associated protein, having a novel key role of the protein in vascular endothelial cells.

Background: Intracranial aneurysms (IA) frequently cause subarachnoid hemorrhage (SAH) and have poor prognosis. However, the molecular mechanisms and diagnostic biomarkers associated with IA and ruptured IA (rIA) remain poorly understood. Methods: In this study, single-cell and transcriptome datasets were obtained from the GEO database. The cell populations were annotated to identify potential pathogenic subpopulations, followed by intercellular communication, pseudotime, and SCENIC analyses. Proteome-wide and transcriptome-wide Mendelian randomization (MR) analyses were conducted to identify risk factors for IA and SAH. The major pathological changes and diagnostic biomarkers of IA and SAH were identified based on the transcriptome datasets. A clinical cohort was established to identify the diagnostic biomarkers and validate the results. Results: Macrophages and neutrophils were predominantly increased in IA and rIA tissues, and neutrophils were markedly upregulated in the blood of SAH patients. SPP1⁺ Macrophage was progressively elevated in aneurysms, promoting vascular smooth muscle cell (VSMC) phenotypic transformation and collagen matrix remodeling through the SPP1 and TGF-β pathways. Furthermore, HIF1α regulon was enriched in SPP1⁺ Macrophage, mediating inflammation and metabolic reprogramming, which contributed to IA progression. Integrated MR analysis identified CD36 as a risk factor for both IA and SAH, and it has been recognized as an effective blood biomarker for SAH. Neutrophils and their related indicators have emerged as excellent biomarkers of SAH in clinical cohorts. Conclusion: This study highlighted the detrimental role of SPP1⁺ Macrophage in IA and SAH using single-cell sequencing and MR analyses. CD36 was identified as a risk factor for IA and SAH and was also an efficient blood biomarker for SAH. In a clinical cohort, neutrophils and related indicators were valuable for the early diagnosis of SAH.

Introduction: As one of the most common complications of diabetes, diabetic cardiomyopathy (DCM) is the main cause of heart failure in patients with diabetes. However, the lack of effective treatments for DCM remains a clinical challenge. (Pro) renin receptor (PRR) is a member of renin angiotensin aldosterone system (RAAS). Here, we aim to determine whether PRR is involved in myocardial pyroptosis in diabetic cardiomyopathy.Methods: We established diabetic rats model by intraperitoneal injection of streptozotocin (STZ). PRR overexpression adenovirus or PRR knockdown adenovirus was injected into the tail vein. Western blot, histopathology and immunohistochemistry staining, ELISA and Echocardiography were used to detect cardiac function changes and myocardial injury levels of DCM rats. Primary cardiomyocytes were stimulated with high glucose and PRR overexpression or PRR knockdown was achieved by adenovirus transfection, we also used the inhibitor of AMPK to decrease the activity of AMPK. Western blot, Real-time PCR, Immunofluorescence and ELISA were used to detect the level of PRR and pyroptosis in cardiomyocyte.Results: We found that high glucose increased the expression of PRR in heart. After overexpression of PRR, the expression of the pyroptosis related proteins such as Caspase-1, IL-1β, IL-18, and NLRP3 was significantly increased, the phosphorylation level of AMPK was significantly decreased, and the fibrosis level was significantly increased, thus aggravating the cardiac function injury of DCM. On the contrary, PRR knockdown can alleviate the level of myocardial pyroptosis in DCM and improve cardiac function. The related mechanism was that PRR could inhibit AMPK phosphorylation and promote the activation of NLRP3 inflammasome.Discussion: PRR aggravated pyroptosis of cardiomyocyte, increased the dysfunction of cardiomyocyte, and may be related to the decrease of AMPK phosphorylation and the overactivation of NLRP3. This may provide new ideas and targets for the treatment of DCM.

Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.