In Vitro Modeling of Age-Associated Lipid Mediator's Impact on Vascular Biology Following Platelet Concentrate...

Lipidomic analysis enables the detailed characterization of platelet concentrates from donors of different ages, offering valuable insights into the role of lipid mediators in aging and transfusion-related adverse reactions (AR). In this study, we analyzed lipidomic profiles from a cohort of single-donor apheresis platelet concentrates, classified into three age groups: 20-44, 45-59, and 60-70 years. Total levels of LPC, LPA, S1P, and eicosanoids did not exhibit significant age-related changes. However, LPA 18:1, LPC 18:1, and S1P levels decreased with advancing age. When examining the relationship between different age groups and their association with AR, we found that LPA, LPC, and eicosanoids are associated with AR in an age-dependent manner. Based on these findings, we investigated the effect of age-related levels of LPA, LPC, and S1P on platelet and endothelial cell biology. These lipid mediators were found to modulate platelet activation, as demonstrated by increased expression of P-selectin, phosphatidylserine, platelet aggregation, as well as endothelial activation, marked by elevated expression of ICAM-1, VCAM-1, and CD40. Our findings present a comprehensive lipidomic profile of single-donor apheresis platelet concentrates across various age groups, highlighting several lipid mediators that may be implicated in aging and AR.