Since December 2019, coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in considerable morbidity and mortality in more than 30 countries worldwide. Recently, COVID-19–associated clusters of severe respiratory illness have been independently associated with risk of mortality, and mounting evidence substantiates the presence of cardiac injury in patients with COVID-19.^1,2 Although a recent study reported that 12% of patients had COVID-19–associated acute cardiac injury,¹ manifesting as an ejection fraction decline and troponin I elevation, and the American College of Cardiology clinical bulletin has highlighted the cardiac implications of COVID-19,³ the association between COVID-19–associated cardiac injury and risk of mortality remains unclear. The present study therefore retrospectively analyzed data from a single center in Wuhan, China, to examine the potential association between cardiac injury and mortality among patients with COVID-19.

Atherosclerosis is a complex systemic inflammatory metabolic disease, which originates from endothelial dysfunction and progresses through plaque formation involving vascular smooth muscle cells (VSMCs) and macrophage uptake of modified low-density lipoprotein (LDL). These processes lead to vascular stenosis, plaque rupture, and potentially sudden death. Metabolic dysregulation and cellular remodeling are fundamental to the pathogenesis of atherosclerosis. In this review, we summarize recent advances in the metabolic reprogramming of major cell types (including endothelial cells, VSMCs, and macrophages) during atherosclerosis progression. Furthermore, we discuss the crosstalk among these cells mediated by such metabolic alterations. Finally, we highlight the implications of metabolic reprogramming for targeted therapeutic strategies, offering insights for precision intervention in aortic atherosclerosis.

Aims Prostaglandin E₂ (PGE2) is involved in the development of cardiac hypertrophy. However, whether PGE2 regulates the chronic kidney disease‐associated cardiac hypertrophy and the tentative mechanism remains to be elucidated. Methods and results We explored the effect of PGE2 receptor inhibitors on cardiac hypertrophy in vitro and in a 5/6 nephrectomy (5/6NT) rat model using quantitative reverse transcription polymerase chain reaction, western blotting, enzyme‐linked immunosorbent assay, immunohistochemical staining, and immunofluorescence staining assays. The result showed that EP2 and EP4 receptors were both up‐regulated in the PGE2‐treated cardiomyocyte cells. PGE2 treatment enhanced active β‐catenin (non‐phosphorylated) signalling through mediating EP2 and EP4 receptors. Interestingly, inhibition of EP2 receptor suppressed PGE2‐induced cardiomyocyte hypertrophy and cardiac fibrosis‐related proteins in vitro. In the 5/6NT rat model, the increased secretion PGE2 was identified in the 5/6NT rat model for 2 weeks (P = 0.0251). EP2 receptor inhibitor administration significantly improved the cardiac function and fibrosis in 5/6NT rats. Conclusions Our study demonstrated that inhibition of EP2 receptor could improve PGE2‐induced cardiac hypertrophy in 5/6NT rats. The exploration of these mechanisms may contribute to the optimization of therapy in chronic kidney disease accompanied cardiac hypertrophy in clinic.

Despite the clinical efficacy of doxorubicin (DOX), effective strategies to prevent its cardiotoxicity are still lacking. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), has demonstrated cardioprotective properties; however, its role and mechanism in DOX-induced cardiotoxicity (DIC) remain unclear. In this study, Finerenone treatment was found to significantly alleviate DOX-induced cardiac dysfunction and pathological remodeling in both mouse models and cultured cells. Mechanistically, molecular docking suggests that Finerenone may directly bind to Latent Transforming Growth Factor Beta Binding Protein 2 (LTBP2), a key regulator of TGF-β bioavailability. This potential binding could inhibit the LTBP2–TGF-β axis, thereby suppressing DOX-induced activation and subsequent Smad3 phosphorylation. The importance of this pathway was supported by the similar anti-fibrotic effects observed with the TGF-β inhibitor LY2109761. However, our findings on the direct binding of Finerenone to LTBP2 are preliminary and require further validation through additional experimental approaches. These results identify LTBP2 as a novel direct target of Finerenone and reveal an additional mechanism underlying its cardioprotective action, suggesting its potential repurposing for the prevention of DIC.

Introduction: Atherosclerosis is a vascular disease whose pathogenesis involves complex transcriptional and post-transcriptional regulation. Conventional bulk RNA-seq captures gene-level expression but does not fully resolve isoform diversity and RNA regulatory features. Methods: Male apolipoprotein E-deficient mice were fed normal chow (NC) or a Western diet (AS) for 16 weeks to establish diet-induced atherosclerosis. Aortic tissues were analyzed by direct RNA sequencing (DRS), bulk RNA-seq, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq). DRS data were used to reconstruct and quantify isoforms and to assess differential transcript expression, RNA modification, alternative splicing, alternative polyadenylation, and poly(A) tail length. Results: DRS generated a full-length aortic transcriptome comprising 35,587 transcripts, including 18,081 novel transcripts and 1,727 differentially expressed transcripts (DETs). Genes corresponding to known DETs were predominantly enriched in immune and inflammatory processes, whereas genes corresponding to novel DETs were primarily associated with lipid metabolism. Integration of ATAC-seq and DRS identified 13 DETs linked to altered chromatin accessibility. DRS further revealed extensive remodeling of RNA modifications, alternative splicing, and 3′-end processing, including dynamic changes in N6-methyladenosine, 5-methylcytosine, and adenosine-to-inosine. Additionally, 459 differential alternative splicing events and 1,320 differential polyadenylation sites were identified. A total of 613 genes exhibited altered 3′untranslated region length with coordinated shifts in poly(A) tail length. Discussion: By integrating DRS with bulk RNA-seq and ATAC-seq, this study establishes a multi-layered landscape of RNA transcriptional and post-transcriptional regulation in atherosclerosis. These findings provide a resource for future mechanistic investigations and for the development of RNA-targeted strategies in vascular disease.

Atherosclerosis, a primary cause of ischemic diseases, is driven by excessive oxidative stress. Edaravone Dexborneol, a clinically used antioxidant, has demonstrated potent protective effects in cerebral ischemia. However, its role in atherosclerosis remains unexplored. In this study, atherosclerosis models were constructed using Apoe-/- mice fed a high-fat diet. Edaravone Dexborneol treatment significantly attenuated aortic atherosclerosis progression, evidenced by reduced advanced plaque burden and improved hemodynamic parameters at the aortic root. The treatment also suppressed oxidative stress, leading to decreased low-density lipoprotein (LDL) oxidation and reduced oxidized LDL (ox-LDL) accumulation in aortic tissues and endothelial cells. Mechanistically, RNA sequencing and Western blot analyses revealed that Edaravone Dexborneol alleviates oxidative damage by activating peroxisome proliferator-activated receptor gamma (PPARγ) and upregulating paraoxonase 1 (PON1) expression. In human umbilical vein endothelial cells (HUVECs), PON1 knockdown partially abolished the antioxidant effects of Edaravone Dexborneol, while PPARγ inhibition reversed its induction of PON1. Furthermore, the combination of Edaravone Dexborneol with Rosuvastatin exhibited synergistic anti-atherogenic effects superior to Rosuvastatin alone. In conclusion, Edaravone Dexborneol attenuates atherosclerosis via the PPARγ/PON1 pathway, highlighting its potential as an antioxidant-based therapeutic strategy for atherosclerotic disease.