A shift in the platelet lipidome correlates with platelet differentiation into distinct subfractions in patients with pulmonary embolism

Abstract

Abstract Aims Severity of pulmonary embolism (PE) is significantly driven by right ventricular (RV) failure and thrombus composition, which possibly alters susceptibility towards therapy. Following platelet activation, platelets differentiate into different phenotypes, including a procoagulant and an aggregatory phenotype. Differentiation into these phenotypes is associated with changes in the platelet lipidome. Hence, we sought to investigate platelet subpopulations and the platelet lipidome in patients with acute PE and concomitant vs. absent RV distress. Methods and results We examined isolated platelets from 48 patients with acute PE. PE and RV distress were diagnosed with CT pulmonary angiogram (CTPA) and transthoracic echocardiography, respectively. We identified platelet subpopulations based on platelet surface exposure of CD42b, phosphatidylserine and GPIIb/IIIa using flow cytometry. Additionally, the platelet lipidome was characterized via HPLC-ESI-QTOF-MS/MS. In patients with RV distress, we found higher levels of aggregatory (P = 0.021) and lower levels of procoagulant platelets (P = 0.033) when compared with patients without RV dysfunction. Moreover, we found a significant upregulation of cholesteryl esters, triglycerides and fatty acyls in platelets of PE patients with RV dysfunction compared to PE patients with normal RV. Finally, a significant correlation of lipids with levels of aggregatory and procoagulant platelets was observed in the overall cohort of patients. Conclusion Specific stimuli can activate distinct metabolic programmes, leading to remodelling of the platelet lipidome that may influence the differentiation of platelets into separate phenotypic subpopulations in PE.