Increased selenium and decreased iron levels in relation to risk of coronary artery disease in patients with diabetes.

Background: Observational studies have reported inconsistent associations between micronutrient levels and the risk of coronary artery disease (CAD) in diabetic patients. We aim to explore the causal association between genetically predicted concentrations of micronutrients (phosphorus, magnesium, selenium, iron, zinc, and copper) and CAD in patients with diabetes. Methods: Single nucleotide polymorphisms (SNPs) connected to serum micronutrient levels were extracted from the corresponding published genome-wide association studies (GWASs). Summary-level statistics for CAD in diabetic patients were obtained from a GWAS of 15,666 patients with diabetes. The primary analysis was carried out with the inverse variance weighted approach, and sensitivity analyses using other statistical methods were further employed to assess the robustness of the results. Results: Genetically predicted selenium level was causally associated with a higher risk of CAD in diabetic patients (odds ratio [OR]: 1.25; 95% confidence interval [CI]: 1.10-1.42; p = 5.01 × 10-4). While, genetically predicted iron concentrations in patients with diabetes were inversely associated with the risk of CAD (OR: 0.82; 95% CI: 0.75-0.90; p = 2.16 × 10-5). The association pattern kept robust in most sensitivity analyses. Nominally significant associations were observed for magnesium and copper with the risk of CAD in patients with diabetes. No consistent evidence was found for the causal associations between phosphorus and zinc levels, and the risk of CAD in patients with diabetes. Conclusion: We provide consistent evidence for the causal effect of increased selenium and decreased iron levels on CAD in patients with diabetes, highlighting the necessity of micronutrient monitoring and application in these patients.

DHX9 Strengthens Atherosclerosis Progression By Promoting Inflammation in Macrophages.

Atherosclerosis (AS) is the main cause of cerebrovascular diseases, and macrophages play important roles in atherosclerosis. DExH-Box helicase 9 (DHX9), as a member of DExD/H-box RNA helicase superfamily II, is identified as an autoantigen in the sera of systemic lupus erythematosus patients to trigger inflammation. The aim of this study was to investigate whether DHX9 is involved in AS development, especially in macrophages-mediated-inflammatory responses. We find that DHX9 expression is significantly increased in oxLDL or interferon-γ-treated macrophages and peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Knockdown of DHX9 inhibits lipid uptake and pro-inflammatory factors expression in macrophages, and ameliorates TNF-α-mediated monocyte adhesion capacity. Furthermore, we find that oxLDL stimulation promotes DHX9 interaction with p65 in macrophages, and further enhances the transcriptional activity of DHX9-p65-RNA Polymerase II complex to produce inflammatory factors. Moreover, using ApoE -/- mice fed with western diet to establish AS model, we find that knockdown of DHX9 mediated by adeno-associated virus-Sh-DHX9 through tail vein injection evidently alleviates AS progression in vivo. Finally, we also find that knockdown of DHX9 inhibits p65 activation, inflammatory factors expression, and the transcriptional activity of p65-RNA Polymerase II complex in PBMCs from patients with CAD. Overall, these results indicate that DHX9 promotes AS progression by enhancing inflammation in macrophages, and suggest DHX9 as a potential target for developing therapeutic drug.

Causal association between sleep traits and the risk of coronary artery disease in patients with diabetes.

Background and aims: The association between sleep traits and coronary artery disease (CAD) in patients with diabetes has been reported in previous observational studies. However, whether these potential relationships are causal remains unclear. We aim to assess the causal relationship between sleep traits and CAD in diabetic. Methods: Genetic instrumental variables associated with five sleep-related traits (insomnia, sleep duration, ease of getting up, morningness and snoring) were extracted from corresponding genome-wide association studies (GWAS). The associations of genetic variants with CAD were based on 15,666 individuals with diabetes (3,968 CAD cases and 11,696 controls). The primary analysis was derived using the inverse variance weighting method. Further sensitivity analysis was conducted to confirm the robustness and consistency of the main results. Results: Genetic liability to insomnia was significantly related to the increased risk of CAD in individuals with diabetes [odds ratio (OR): 1.163; 95% CI: 1.072-1.254; p = 0.001]. Suggestive evidence was found for the borderline associations between both sleep duration (OR: 0.629; 95% CI: 0.380-1.042, p = 0.072) and snoring (OR: 1.010, 95% CI: 1.000-1.020, p = 0.050) with CAD risk. However, no consistent evidence was found for the association between ease of getting up and morningness with the risk of CAD in diabetic. Similar results can be verified in most sensitivity analyses. Conclusions: We provide consistent evidence for the causal effect of insomnia on the increased risk of CAD in individuals with diabetes. The management of sleep health should be emphasized to prevent CAD in diabetic patients.