A distinctive feature of ferroptosis is intracellular iron accumulation and the impairment of antioxidant capacity, resulting in a lethal accumulation of lipid peroxides leading to cell death. This study was conducted to determine whether inhibiting isocitrate dehydrogenase 1 (IDH1) may help to prevent foam cell formation by reducing oxidized low-density lipoprotein (ox-LDL)-induced ferroptosis in macrophages and activating nuclear factor erythroid 2-related factor 2 (NRF2). Gene expression profiling (GSE70126 and GSE70619) revealed 21 significantly different genes, and subsequent bioinformatics research revealed that ferroptosis and IDH1 play essential roles in foam cell production. We also confirmed that ox-LDL elevates macrophage ferroptosis and IDH1 protein levels considerably as compared with controls. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, reduced ox-LDL-induced elevated Fe2+ levels, lipid peroxidation (LPO) buildup, lactate dehydrogenase (LDH) buildup, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4), ferritin heavy polypeptide 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11) protein downregulation. More crucially, inhibiting IDH1 reduced Fe2+ overload, lipid peroxidation, LDH, and glutathione depletion, and elevated GPX4, FTH1, and SLC7A11 protein expression, resulting in a reduction in ox-LDL-induced macrophage ferroptosis. IDH1 inhibition suppressed ox-LDL-induced macrophage damage and apoptosis while raising NRF2 protein levels. We have demonstrated that inhibiting IDH1 reduces ox-LDL-induced ferroptosis and foam cell formation in macrophages, implying that IDH1 may be an important molecule regulating foam cell formation and may be a promising molecular target for the treatment of atherosclerosis.

There is an ongoing debate concerning the optimal surgical option of myocardial revascularization for octogenarians. The current meta‐analysis aimed to compare clinical outcomes following off‐pump coronary artery bypass grafting (OPCABG) or conventional coronary artery bypass grafting (CCABG) in octogenarians. PubMed, Cochrane, Web of Science, and EMBASE databases were searched to identify eligible studies from inception to March 2021. The analysis was performed using STATA 15.1. A literature search yielded 18 retrospective studies involving 146 372 patients (OPCABG = 44 522 vs. CCABG = 101 850). Pooled analysis showed a strong trend toward reducing mortality risk in the OPCABG group (odds ratio: 0.75, 95% confidence interval: 0.56–1.00, p = .05). However, it did not reach statistical significance. The sensitive analysis demonstrated that OPCABG was less likely to cause death than CCABG. There were comparable data in myocardial infarction, renal failure, deep sternal wound infection, and hospital stays between the two groups, although the incidence of stroke, atrial fibrillation, prolonged ventilation, and reoperation for bleeding was significantly lower in the OPCAGB group. OPCABG may be an effective surgical strategy for myocardial revascularization, especially in reducing the incidence of postoperative stroke, atrial fibrillation, prolonged ventilation, and reoperation for bleeding.

Atherosclerosis (AS) is one of the leading causes of death among the elderly, and is primarily caused by foam cell generation and macrophage inflammation. Rutin is an anti-inflammatory, anti-oxidant, anti-allergic, and antiviral flavonoid molecule, known to have anti-atherosclerotic and autophagy-inducing properties, but its biological mechanism remains poorly understood. In this study, we uncovered that rutin could suppress the generation of inflammatory factors and reactive oxygen species (ROS) in ox-LDL-induced M2 macrophages and enhance their polarization. Moreover, rutin could decrease foam cell production, as shown by oil red O staining. In addition, rutin could increase the number of autophagosomes and the LC3II/I ratio, while lowering p62 expression. Furthermore, rutin could significantly inhibit the PI3K/ATK signaling pathway. In summary, rutin inhibits ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling, showing potential in treating atherosclerosis.