Identification of key lipids critical for platelet activation by comprehensive analysis of the platelet lipidome

Abstract

Platelet integrity and function critically depend on lipid composition. However, the lipid inventory in platelets was hitherto not quantified. Here, we examined the lipidome of murine platelets using lipid-category tailored protocols on a quantitative lipidomics platform. We could show that the platelet lipidome comprises almost 400 lipid species and covers a concentration range of 7 orders of magnitude. A systematic comparison of the lipidomics network in resting and activated murine platelets, validated in human platelets, revealed that <20% of the platelet lipidome is changed upon activation, involving mainly lipids containing arachidonic acid. Sphingomyelin phosphodiesterase-1 (Smpd1) deficiency resulted in a very specific modulation of the platelet lipidome with an order of magnitude upregulation of lysosphingomyelin (SPC), and subsequent modification of platelet activation and thrombus formation. In conclusion, this first comprehensive quantitative lipidomic analysis of platelets sheds light on novel mechanisms important for platelet function, and has therefore the potential to open novel diagnostic and therapeutic opportunities.

LipidCreator workbench to probe the lipidomic landscape

“…Supplementing the fully accessible workbench, we also prepared predefined transition lists for several model system lipidomes, such as yeast, mouse (platelets, heart, brain hippocampus), drosophila and human (plasma, platelets) [32][33][34][35][36] , making it straightforward to start a targeted lipidomics experiment.…”

“…Several reported lipidome compositions from the literature were used to determine the coverage provided by LipidCreator ( Fig. 4) for the following organisms and tissues: (a) Human plasma 40 , (b) Human platelet 36 , (c) Mouse heart 35 , (d) Mouse platelet 36 , (e) Mouse brain 32,41 , (f) Yeast 34 , (g) Zebrafish 42 , (h) Drosophila 33,43 , (i) Arabidopsis 44 , and (j) E. coli [45][46][47] . We can show that the vast majority of reported lipids among the selected model organisms are supported by LipidCreator.…”

Goslin - A Grammar of Succinct Lipid Nomenclature

“…Currently, we are working on several improvements of the library, 1) to offer an implementation of Goslin in additional programming languages (e.g., C#); 2) to improve the performance of the existing implementations; and 3) to add more structural lipid classes and categories into the grammar for a higher coverage of lipids. We already applied Goslin in other recent projects (16,17) and achieved a high performance boost especially when exchanging our lipid lists with our collaboration partners. The Goslin implementations are freely available under https://github.com/lifs-tools/ goslin under the terms of liberal open source licenses.…”

Platelet lipidome: Dismantling the “Trojan horse” in the bloodstream

“…PCs, PEs, PGs, SM, and cardiolipin span a range of > two orders of magnitude; some ceramides and free‐FAs reach > four orders of magnitude, while plasmanyl/plasmalogen‐PC are limited. This study claims that the platelet lipidome is altered <20% upon activation for 5 minutes. Another study demonstrates that collagen stimulation of murine platelets enhances free‐FAs‐(31%), LPC‐(57%), LPE‐(38%), and DGs‐(21%).…”

“…Moreover, the non‐annotated lipids available in the public domain offers an opportunity for further discovery . Ahrends's group explored the murine and human platelet lipidome showing PE, PC, SM, PS, and PI as the most abundant species and that only 15 lipids constitute 70% of the entire lipid mass . PCs, PEs, PGs, SM, and cardiolipin span a range of > two orders of magnitude; some ceramides and free‐FAs reach > four orders of magnitude, while plasmanyl/plasmalogen‐PC are limited.…”