Search

Although observational studies have linked primary aldosteronism (PA) with cardiovascular diseases (CVDs), the causality remains uncertain. In this study, we aimed to investigate whether PA is causally associated with CVD risk and cardiac magnetic resonance (CMR) parameters using the Mendelian randomization (MR) method. Independent and genome‐wide significant single nucleotide polymorphisms for PA were extracted from genome‐wide association study (GWAS) summary statistics. Genetic associations with the CVDs and CMR parameters were obtained from recent large‐scale GWASs or genetic consortia. Inverse‐variance weighted (IVW) method was utilized for the preliminary estimates, and multiple sensitivity analyses (including weighted median, Cochran's Q test, MR‐Egger, MR‐PRESSO, and leave‐one‐out analysis) were conducted to verify the robustness of the results. The MR analyses using the IVW method showed that genetically predicated PA was significantly associated with atrial fibrillation (OR = 1.046, 95% CI: 1.029–1.062, padj < 0.001), myocardial infarction (OR = 1.029, 95% CI: 1.005–1.053, padj = 0.027), heart failure (OR = 1.023, 95% CI: 1.004–1.042, padj = 0.027), any stroke (OR = 1.062, 95% CI: 1.031–1.095, padj < 0.001), any ischemic stroke (OR = 1.058, 95% CI: 1.022–1.095, padj = 0.004), and small vessel stroke (OR = 1.116, 95% CI: 1.041–1.196, padj = 0.004). Notably, PA also had a causal effect on adverse cardiac remodeling, including larger ventricular and atrial volumes, higher ventricular stroke volume, and reduced left atrial emptying fraction. Our findings support a causal role of PA in higher cardiovascular disease risk and adverse cardiac remodeling. Given the diagnostic delay and disease burden in PA, more attention should be paid to the screening and treatment of PA to reduce the incidence of cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Background: Copper is an essential trace element for biological systems, as it plays a critical role in the activity of various enzymes and metabolic processes. However, the dysregulation of copper homeostasis is closely associated with the onset and progression of numerous diseases. In recent years, copper‐induced cell death, a novel form of cellular demise, has garnered significant attention. This process is characterized by the abnormal accumulation of intracellular copper ions, leading to cellular dysfunction and eventual cell death. Copper toxicity occurs through the interaction of copper with acylated enzymes in the tricarboxylic acid (TCA) cycle. This interaction results in subsequent protein aggregation, causing proteotoxic stress and ultimately resulting in cell death. Despite the promise of these findings, the detailed mechanisms and broader implications of cuproptosis remain underexplored. Therefore, our study aimed to investigate the role of copper in cell death and autophagy, focusing on the molecular mechanisms of cuproptosis. We also aimed to discuss recent advancements in copper‐related research across various diseases and tumors, providing insights for future studies and potential therapeutic applications. Main Body: This review delves into the biological significance of copper metabolism and the molecular mechanisms underlying copper‐induced cell death. Furthermore, we discuss the role of copper toxicity in the pathogenesis of various diseases, emphasizing recent advancements in the field of oncology. Additionally, we explore the therapeutic potential of targeting copper toxicity. Conclusion: The study highlights the need for further research to explore alternative pathways of copper‐induced cell death, detailed mechanisms of cuproptosis, and biomarkers for copper poisoning. Future research should focus on exploring the molecular mechanisms of cuproptosis, developing new therapeutic strategies, and verifying their safety and efficacy in clinical trials. [ABSTRACT FROM AUTHOR]

Epidemiological studies have shown an association between type 2 diabetes (T2D) and calcific aortic valve stenosis (CAVS), but the potential causal relationship and underlying mechanisms remain unclear. Therefore, we conducted a two-sample and two-step Mendelian randomization (MR) analysis to evaluate the association of T2D with CAVS and the mediating effects of circulating metabolites and blood pressure using genome-wide association study (GWAS) summary statistics. The inverse variance weighted (IVW) method was used for the primary MR analysis, and comprehensive sensitivity analyses were performed to validate the robustness of the results. Our results showed that genetically predicted T2D was associated with increased CAVS risk (OR 1.153, 95% CI 1.096–1.214, p < 0.001), and this association persisted even after adjusting for adiposity traits in multivariable MR analysis. Furthermore, the two-step MR analysis identified 69 of 251 candidate mediators that partially mediated the effect of T2D on CAVS, including total branched-chain amino acids (proportion mediated: 23.29%), valine (17.78%), tyrosine (9.68%), systolic blood pressure (8.72%), the triglyceride group (6.07–11.99%), the fatty acid group (4.78–12.82%), and the cholesterol group (3.64–11.56%). This MR study elucidated the causal impact of T2D on CAVS risk independently of adiposity and identified potential mediators in this association pathways. Our findings shed light on the pathogenesis of CAVS and suggest additional targets for the prevention and intervention of CAVS attributed to T2D. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI), a severe outcome of cardiovascular disease, poses a serious threat to human health. Uncontrolled inflammation and excessive cardiomyocyte death, following an infarction event, significantly contribute to both the mortality rate and complications associated with MI. The protein IL-4-induced gene 1 (IL4I1 or FIG1) serves as a natural inhibitor of innate and adaptive immunity, playing a crucial role in CD4+ T cell differentiation, macrophage polarization, and ferroptosis inhibition. Previous studies have linked IL4I1 to acute MI. This review summarizes evidence from both basic and clinical research, highlighting IL4I1 as a critical immunoregulatory enzyme that not only regulates inflammatory responses, but also potentially mitigates MI-induced damage., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)