Lipids and Antiplatelet Therapy: Important Considerations and Future Perspectives

Abstract

Lipids play an essential role in platelet functions. It is known that polyunsaturated fatty acids play a role in increasing platelet reactivity and that the prothrombotic phenotype plays a crucial role in the occurrence of major adverse cardiovascular events. The ongoing increase in cardiovascular diseases’ incidence emphasizes the importance of research linking lipids and platelet function. In particular, the rebound phenomenon that accompanies discontinuation of clopidogrel in patients receiving dual antiplatelet therapy has been associated with changes in the lipid profile. Our many years of research underline the importance of reduced HDL values for the risk of such a rebound effect and the occurrence of thromboembolic events. Lipids are otherwise a heterogeneous group of molecules, and their signaling molecules are not deposited but formed “on-demand” in the cell. On the other hand, exosomes transmit lipid signals between cells, and the profile of such changes can be monitored by lipidomics. Changes in the lipid profile are organ-specific and may indicate new drug action targets.

CYP2C19 polymorphisms and lipoproteins associated with clopidogrel resistance in children with Kawasaki disease in China: A prospective study

“…Lipoproteins can influence platelet count and characteristics and modulate the risk of atherothrombosis via the megakaryocyte-platelet hemostatic axis ( 34 ). In the present study it was found that HDL was a protective factor for the occurrence of CR in children with KD.…”

“…Similarly, another study found that low HDL levels were associated with CR in CAD patients ( 36 ). Moreover, it was shown that patients with low HDL levels might be more prone to platelet hyperreactivity in the period after clopidogrel cessation ( 34 ), and the infusion of reconstituted HDL was highly effective in inhibiting platelet hyperactivity in diabetic patients ( 37 ). However, a study of ACS patients undergoing PCI suggested that HDL was inversely associated with platelet activation parameters but not with clopidogrel response variability ( 38 ).…”

“…Although the specific mechanism of the effect of HDL on the antiplatelet effect of clopidogrel is still unclear, it is generally considered that in addition to its role in reverse cholesterol transport, HDL also inhibits platelet activation in vivo and in vitro to mediate antithrombotic effects ( 39 ). Studies have shown that HDL can prevent platelet hyperreactivity by limiting the excessive accumulation of cholesterol in platelet membranes and regulating platelet signaling pathways by binding specific receptors on the platelet surface ( 34 , 39 ). Meanwhile, HDL also stimulates the endothelial production of nitric oxide and prostacyclin, which are potent inhibitors of platelet activation ( 39 ).…”

Lysophosphatidylethanolamine Affects Lipid Accumulation and Metabolism in a Human Liver-Derived Cell Line

“…Lysophosphatidylethanolamine (lysoPE) is a lysophospholipid that is a deacylated product of phosphatidylethanolamine (PE) hydrolysis induced by phospholipase A1/A2 [ 1 ]. LysoPE is a minor component of the cell membrane [ 2 ] and stimulates chemotactic migration and infiltration of ovarian cancer cells [ 3 ].…”

“…Therefore, the aims of our study were (1) to investigate the physiological functions of lysoPE, targeting its effect on lipid accumulation in human hepatocytes; (2) to explore the modulation of intracellular lipid metabolism, including the changes in lipid content and the alterations of molecular composition and (3) to analyze the expression of the genes related to lipid metabolism and catabolism. The graphical representation of the present study workflow is shown in the supplementary data (Scheme S1).…”