Influence of Antiplatelet Agents on the Lipid Composition of Platelet Plasma Membrane: A Lipidomics Approach with Ticagrelor and Its Active Metabolite

Abstract

Lipids contained in the plasma membrane of platelets play an important role in platelet function. Modifications in the lipid composition can fluidify or rigidify the environment around embedded receptors, in order to facilitate the access of the receptor by the drug. However, data concerning the lipid composition of platelet plasma membrane need to be updated. In addition, data on the impact of drugs on plasma membrane composition, in particular antiplatelet agents, remain sparse. After isolation of platelet plasma membrane, we assessed, using lipidomics, the effect of ticagrelor, a P2Y12 antagonist, and its active metabolite on the lipid composition of these plasma membranes. We describe the exact lipid composition of plasma membrane, including all sub-species. Ticagrelor and its active metabolite significantly increased cholesterol and phosphatidylcholine ether with short saturated acyl chains 16:0/16:0, and decreased phosphatidylcholine, suggesting overall rigidification of the membrane. Furthermore, ticagrelor and its active metabolite decreased some arachidonylated plasmalogens, suggesting a decrease in availability of arachidonic acid from the membrane phospholipids for synthesis of biologically active mediators. To conclude, ticagrelor and its active metabolite seem to influence the lipid environment of receptors embedded in the lipid bilayer and modify the behavior of the plasma membrane.

Tannins as Hemostasis Modulators

“…Data on the impact of plasma membrane fluidity in platelet activity are inconsistent. On the one hand, the antiplatelet drugs like ASA or ticagrelor rise the rigid of the platelets plasma membrane ( Watała and Gwoździński, 1993 ; Lagoutte-Renosi et al, 2021 ) and platelets from type 1 diabetic patients have increased fluidity of the membrane ( Mazzanti et al, 1997 ). On the other hand, platelet membrane is less fluid in patients who have hypertension, diabetes and also smoke ( Nanetti et al, 2008 ).…”

Platelet Membrane: An Outstanding Factor in Cancer Metastasis

“…Lipidomics studies have reported that the lipid composition of the platelet membrane is crucial for the functioning of the cell. The lipid composition of the platelet membrane is responsible for a series of phenomena, such as the shape, curvature, and flexibility of the membrane and the flux of molecules through it [93,94]. It has also been shown that changes in the lipid composition of the platelet membrane induce structural and functional modifications such as activation, degranulation, and exocytosis processes [93,94].…”

“…(2) Skeaff and Holub [96] reported that, during platelet activation, thrombin, a platelet activator, causes a decrease of up to 45% in the content of phosphatidylinositol in the platelet plasma membrane [96]. (3) Lagoutte-Renosi et al [94] carried out a lipidomics study on resting platelet membranes. Their results showed that the membranes are constituted mainly by phosphatidylcholines (35.2 ± 0.8%), cholesterol (28.35 ± 0.7%), ether-linked phosphatidylethanolamines (10.40 ± 0.2%), sphingomyelins (7.26 ± 0.3%), phosphatidylserine (6.06 ± 0.1%), phosphatidylethanolamines (6.41 ± 0.1%), phosphatidylinositols (2.41 ± 0.03%), and ether-linked phosphatidylcholine (1.84 ± 0.04%) [94].…”

Fundamentals of Membrane Lipid Replacement: A Natural Medicine Approach to Repairing Cellular Membranes and Reducing Fatigue, Pain, and Other Symptoms While Restoring Function in Chronic Illnesses and Aging

“…The actions of various agents and drugs can affect the compositions of plasma membranes and in the process change their functional properties. For example, certain antiplatelet drugs, such as ticagrelor, a membrane P2Y12 antagonist, and its active metabolite significantly increased platelet cholesterol and PC with short FA acyl chains, suggesting platelet membrane rigidification and modification of lipid-receptor interactions involved in ADP-induced platelet activation [37].…”