Circulating Inflammatory Mediators and Genetic Polymorphisms of Inflammation Mediators and Their Association with Factors Related to Abdominal Aortic Aneurysm: A Systemic Review and Meta-Analysis.

Background: This study aimed to explore the levels of circulating inflammatory factors CRP, IL-6, IL-10 and TNF- α based on the literature review. This study also examined the influence of single nucleotide polymorphism (SNP) sites on the susceptibility of abdominal aortic aneurysm (AAA) using meta-analysis and intended to provide additional information on pathogenesis of AAA research. Methods: Electronic databases including PubMed and Web of Science were systemically searched to collect the information on AAA, inflammatory factors such as CRP, IL-6, IL-10, TNF- α and the SNP sites for data extraction. Altogether six SNPs in four genes (rs3091244, CRP; rs1800947, CRP; rs1205, CRP; rs1800795, IL-6; rs1800896, IL-10; and rs1800629, TNF) were assessed. Results: This study enrolled altogether 41 relevant investigations involving 9,007 AAA patients to carry out meta-analysis. According to pooled analysis, circulating CRP and IL-6 levels were shown to be related to the AAA, while plasma IL-10 and TNF- α levels were not associated with AAA. The circulating CRP level standard mean difference (SMD) was 0.30 (95% confidence interval (CI): 0.17-0.43), the IL-6 level SMD was 0.34 (95% CI: 0.20-0.49), the IL-10 level SMD was -0.01 (95% CI: -0.09-0.06), and the TNF- α level SMD was 0.09 (95% CI: 0.00-0.19). Similarly, the odds ratio (OR) of rs3091244 (CRP) under the recessive gene model was 1.70 (95% CI: 1.13-2.57). In addition, individuals with A and T mutant genes at locus rs3091244 might have a higher tendency of AAA susceptibility than those with C allele. Consecutively, the OR was 0.91 (95% CI: 0.51-0.97) for rs1800795 (IL-6) locus in the allele model, and individuals with G mutant gene at locus rs1800795 (IL-6) might be less susceptible to AAA than those with C allele. Meanwhile, the rs1800896 (IL-10) locus had a positive association under the five statistical models, and individuals with A mutant gene at locus rs1800896 might have a higher susceptibility to AAA than those with G allele. Nevertheless, the rs1800947 (CRP), rs1205 (CRP), and rs1800629 (TNF) loci did not have positive correlation under the five statistical models, with no statistical significance. The results indicate that the gene polymorphisms at rs1800629, rs1800947, and rs1205 loci were not related to the AAA susceptibility. Conclusions: Gene polymorphisms in certain known inflammatory mediators related to AAA susceptibility might serve as potential predictive biomarkers for clinical applications. Moreover, SNP of inflammatory mediators relevant to abdominal aortic aneurysmal formation and progression need extensive investigations to confirm these results.

Body mass index and the risk of abdominal aortic aneurysm presence and postoperative mortality: a systematic review and dose-response meta-analysis.

BACKGROUND: The clinical data regarding the relationships between BMI and abdominal aortic aneurysm (AAA) are inconsistent, especially for the obese and overweight patients. The aims of this study were to determine whether obesity is associated with the presence of AAA and to investigate the quantitative relationship between BMI and the risk of AAA presence and postoperative mortality. MATERIALS AND METHODS: PubMed, Web of Science, and Embase databases were used to search for pertinent studies updated to December 2023. The pooled relative risk (RR) with 95% CI was estimated by conventional meta-analysis based on random effects model. Dose-response meta-analyses using robust-error meta-regression (REMR) model were conducted to quantify the associations between BMI and AAA outcome variables. Subgroup analysis, sensitivity analysis, and publication bias analysis were performed according to the characteristics of participants. RESULTS: Eighteen studies were included in our study. The meta-analysis showed a higher prevalence of AAA with a RR of 1.07 in patients with obesity. The dose-response meta-analysis revealed a nonlinear relationship between BMI and the risk of AAA presence. A 'U' shape curve reflecting the correlation between BMI and the risk of postoperative mortality in AAA patients was also uncovered, suggesting the 'safest' BMI interval (28.55, 31.05) with the minimal RR. CONCLUSIONS: Obesity is positively but nonlinearly correlated with the increased risk of AAA presence. BMI is related to AAA postoperative mortality in a 'U' shaped curve, with the lowest RR observed among patients suffering from overweight and obesity. These findings offer a preventive strategy for AAA morbidity and provide guidance for improving the prognosis in patients undergone AAA surgical repair.

Elucidating thoracic aortic dissection pathogenesis: The interplay of m1A-related gene expressions and miR-16-5p/YTHDC1 Axis in NLRP3-dependent pyroptosis.

The underlying molecular mechanisms of thoracic aortic dissection (TAD) remain incompletely understood. Recent insights into RNA methylation and microRNA-mediated gene regulation offer new avenues for exploring how these processes contribute to the pathophysiology of TAD, particularly through the modulation of pyroptosis and smooth muscle cell viability. This research aimed to elucidate the interplay of m1A-related gene expressions and miR-16-5p/YTHDC1 Axis in NLRP3-dependent pyroptosis, a mechanism implicated in the pathogenesis of TAD. We collected tissue samples from 28 human TAD patients and 8 healthy aortic group, as well as utilized a mouse model to replicate the disease. A combination of computational, in vitro, and in vivo methods was applied, including CIBERSORTx analysis, Pearson correlation, gene transfection using antagomiR-16-5p, siRNA, and several staining as well as cell culture techniques. Our analysis indicated two differentially expressed genes, ALKBH2 and YTHDC1. We found significant upregulation of has-miR-16-5p and downregulation of YTHDC1 at mRNA level in AD samples. Immune cell infiltration in TAD samples was examined using the CIBERSORTx database. We confirmed that YTHDC1 was a target of miR-16-5p, as evidenced by an inhibitory effect on luciferase activity. Inhibition of miR-16-5p enhanced SMC proliferation and promoted cell viability whilst downregulating NLRP3-pyroptosis. YTHDC1 expression was increased, and NLRP3-pyroptosis expressions were inhibited, suggesting miR-16-5p/YTHDC1 axis may involve the NLRP3-pyroptosis of the SMC. In vivo analyses confirmed the prevention of NLRP3-pyroptosis in middle layer of the thoracic aorta, implying that the miR-16-5p/YTHDC1 axis regulated SMC proliferation via NLRP3-pyroptosis signaling. Our findings underscored the anti-pyroptotic role of miR-16-5p/YTHDC1 axis in the pathogenesis of TAD, suggesting a potential therapeutic strategy via targeting YTHDC1 and suppressing miR-16-5p to inhibit NLRP3-dependent pyroptosis. Although further investigation is needed, these results relating to SMC proliferation are a significant step forward in understanding TAD.