Globally, cardiovascular disease (CVD) has emerged as a leading cause of mortality. Bisphenol A (BPA), recognized as one of the most prevalent and widely distributed endocrine-disrupting chemicals (EDCs), has been consistently linked to the progression of CVD. This research centers on unraveling the molecular mechanisms responsible for the toxic effects of BPA exposure on CVD. Key targets and pathways involved in action of BPA on CVD were investigated by network toxicology. Binding abilities of BPA to core targets were evaluated by molecular docking. Based on information retrieved from ChEMBL, DrugBank, and OMIM databases, a total of 27 potential targets were found to be associated with the influence of BPA on CVD. Furthermore, the STRING and Cytoscape software were employed to identify three central genes—ESR1, PPARG, and PTGS2—and to construct both the protein-protein interaction network and an interaction diagram of potential targets. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes, KEGG) pathway enrichment analyses via WebGestalt revealed key biological processes (BP), cellular components (CC), molecular functions (MF), and pathways, such as the calcium signaling pathway, inflammatory mediator regulation of TRP channels, gap junction, adrenergic signaling in cardiomyocytes, cGMP-PKG signaling pathway, and cAMP signaling pathway, predominantly involved in BPA-induced CVD toxicity. By using molecular docking investigations, it proved that BPA binds to ESR1, PPARG, and PTGS2 steadily and strongly. This study not only establishes a theoretical framework for understanding the molecular toxicity mechanism of BPA in cardiovascular disease (CVD) but also introduces an innovative network toxicology approach to methodically investigate the influence of environmental contaminants on CVD. This methodology sets the stage for drug discovery efforts targeting CVD linked to exposure to endocrine-disrupting chemicals (EDCs).

The excessive proliferation and migration of vascular smooth muscle cells (VSMCs) are mainly responsible for vascular occlusion diseases, such as pulmonary arterial hypertension and restenosis. Our previous study demonstrated thymoquinone (TQ) attenuated monocrotaline‐induced pulmonary arterial hypertension. The aim of the present study is to systematically examine inhibitory effects of TQ on platelet‐derived growth factor‐BB (PDGF‐BB)–induced proliferation and migration of VSMCs in vitro and neointimal formation in vivo and elucidate the potential mechanisms. Vascular smooth muscle cells were isolated from the aorta in rats. Cell viability and proliferation were measured in VSMCs using the MTT assay. Cell migration was detected by wound healing assay and Transwell assay. Alpha‐smooth muscle actin (α‐SMA) and Ki‐67‐positive cells were examined by immunofluorescence staining. Reactive oxygen species (ROS) generation and apoptosis were measured by flow cytometry and terminal deoxyribonucleotide transferase–mediated dUTP nick end labelling (TUNEL) staining, respectively. Molecules including the mitochondria‐dependent apoptosis factors, matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), PTEN/AKT and mitogen‐activated protein kinases (MAPKs) were determined by Western blot. Neointimal formation was induced by ligation in male Sprague Dawley rats and evaluated by HE staining. Thymoquinone inhibited PDGF‐BB–induced VSMC proliferation and the increase in α‐SMA and Ki‐67‐positive cells. Thymoquinone also induced apoptosis via mitochondria‐dependent apoptosis pathway and p38MAPK. Thymoquinone blocked VSMC migration by inhibiting MMP2. Finally, TQ reversed neointimal formation induced by ligation in rats. Thus, TQ is a potential candidate for the prevention and treatment of occlusive vascular diseases.

Left atrial (LA) remodeling has been identified to predict atrial fibrillation (AF) and heart failure. However, the role of LA diameter (LAD) in patients with heart failure (HF) with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF) remains poorly understood. A total of 142 patients including 71 subjects with AF (21 of HFpEF, 22 of HFmrEF, and 28 of HFrEF) and 71 ejection fraction (EF)-matched subjects with sinus rhythm (SR) were included in the study. Baseline characteristics and echocardiographic parameters including LAD were compared between both groups as well as among HFpEF, HFmrEF, and HFrEF. In receiver-operating characteristic (ROC) analyses, LAD predicted AF in HFpEF, HFmrEF, and HFrEF [area under the curve (AUC): 0.646; P = .03]. LAD was negatively association with left ventricular ejection fraction while positively with Nt-proNP and left ventricular end-diastolic diameter (regression coefficient: −0.239, P = .004; regression coefficient: 0.191, P = .023; regression coefficient: 0.357, P < .001). In ROC analyses, LAD predicted HFrEF among the 3 categories (AUC: 0.629, P = .01). In the setting of HF, LAD was higher in AF than in and SR, and predicted AF. Furthermore, LAD was associated with severity of HF in HFpEF, HFmrEF, and HFrEF, and also predicted HFrEF.

Vitamin C (ascorbic acid) is a nutrient used to treat cardiovascular disease (CVD). However, the pharmacological targets of vitamin C and the mechanisms underlying the therapeutic effects of vitamin C on CVD remain to be elucidated. In this study, we used network pharmacology approach to investigate the pharmacological mechanisms of vitamin C for the treatment of CVD. The core targets, major hubs, enriched biological processes, and key signaling pathways were identified. A protein-protein interaction network and an interaction diagram of core target-related pathways were constructed. Three core targets were identified, including phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, signal transducer and activator of transcription-3 (STAT3), and prothrombin. The GO and KEGG analyses identified top 20 enriched biological processes and signaling pathways involved in the therapeutic effects of vitamin C on CVD. The JAK-STAT, STAT, PD1, EGFR, FoxO, and chemokines signaling pathways may be highly involved in the protective effects of vitamin C against CVD. In conclusion, our bioinformatics analyses provided evidence on the possible therapeutic mechanisms of vitamin C in CVD treatment, which may contribute to the development of novel drugs for CVD.

Graphical Gal-3 triggers myocardial apoptosis, oxidative stress, inflammatory cytokines release, macrophage infiltration, and fibrosis, leading to cardiac dysfunction in DCM mice.