CD19 on CD20- immune cell causes aortic valve calcification by affecting levels of the plasma metabolite 1-(1-enyl-palmitoyl)-2-arachidonoyl-gpc (p-16:0/20:4): a Mendelian Randomization study

Background Immune cells play a significant role in the process of aortic valve calcification (AVC). However, the interactions between AVC and specific immune cell types have yet to be demonstrated. The aim of this study was to investigate the causal relationship between immune cells and AVC, as well as to determine the mediating role of potential plasma metabolites. Methods In this study, publicly available genome-wide association study (GWAS) summary statistics were employed to ascertain the correlation between 731 immune cells and 1400 plasma metabolites with AVC. Firstly, two-sample and reverse Mendelian Randomisation Mendelian Randomization (MR) analyses were conducted to ascertain the causal relationship between immune cells and AVC. Subsequently, a two-step MR analysis demonstrated that the relationship between immune cells and AVC was mediated by plasma metabolites. The robustness of the findings was confirmed by several sensitivity analyses. Results Our study indicate that 42 out of 731 immune cells were correlated with AVC. Among these, immune cell CD19 on CD20- demonstrated a positive correlation with AVC (OR_IVW = 1.0629, OR 95% CI = 1.0259–1.1012, P = 0.0007). Furthermore, immune cell CD19 on CD20- correlated with 47 metabolites, including a positive correlation with plasma 1-(1-alkenyl-palmitoyl)-2-propenoyl-GPC (P-16:0/20:4) levels (OR_IVW = 1.0535, OR 95% CI = 1.0079–1.1010, P = 0.0209). Additionally, 47 metabolites were found to be correlated with AVC. Notably, plasma 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4) levels exhibited a positive correlation with aortic calcification (OR_IVW = 1.0079, OR 95% CI = 1.0221–1.1383, P = 0.0058). Plasma 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4) levels acted as a mediator between CD19 on CD20- and AVC, with a mediation effect size of 0.0039, constituting 6.47% of the total effect. Conclusion The present study is based on a mediated MR analysis, which demonstrates that CD19 on CD20-immune cell cause AVC by affecting plasma 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (p-16:0/20:4) levels. This provides a new perspective on the mechanism of the development of AVC and offers a potential therapeutic target for metabolic intervention.