Targeting the Platelet-Activating Factor Receptor (PAF-R): Antithrombotic and Anti-Atherosclerotic Nutrients

Abstract

Platelet-activating factor (PAF) is a lipid mediator that interacts with its receptor (PAF-R) to carry out cell signalling. However, under certain conditions the binding of PAF to PAF-R leads to the activation of pro-inflammatory and prothrombotic pathways that have been implicated in the onset and development of atherosclerotic cardiovascular diseases (CVD) and inflammatory diseases. Over the past four decades, research has focused on the identification and development of PAF-R antagonists that target these inflammatory diseases. Research has also shown that dietary factors such as polar lipids, polyphenols, and other nutrient constituents may affect PAF metabolism and PAF-R function through various mechanisms. In this review we focus on the inhibition of PAF-R and how this may contribute to reducing cardiovascular disease risk. We conclude that further development of PAF-R inhibitors and human studies are required to investigate how modulation of the PAF-R may prevent the development of atherosclerotic cardiovascular disease and may lead to the development of novel therapeutics.

The Role of Dietary Lipids in Cognitive Health: Implications for Neurodegenerative Disease

“…These include phosphoglycerides, leukotrienes, lysophospholipids, and the phospholipid platelet activating factor (PAF). PAF binds the PAF receptor and triggers downstream activation, thereby regulating processes such as the immune response, cell proliferation and apoptosis, making it an important mediator of these downstream signalling events [ 108 ].…”

The Ex Vivo and In Vitro Antithrombotic Properties of Fermented Irish Ovine Yogurt Drink

“…Platelet-activating factor (PAF) is a phospholipid mediator of inflammation that also induces platelet activation and aggregation. PAF functions by binding to the PAF receptor (PAF-R), a G-protein coupled receptor (GPCR) located on cells involved in immune function [9,10]. The consumption of foods or nutraceuticals rich in bioactive lipids (dietary polar lipids) that target platelet signalling pathways such as thrombin and PAF may be beneficial against inflammatory diseases [10].…”

“…PAF functions by binding to the PAF receptor (PAF-R), a G-protein coupled receptor (GPCR) located on cells involved in immune function [9,10]. The consumption of foods or nutraceuticals rich in bioactive lipids (dietary polar lipids) that target platelet signalling pathways such as thrombin and PAF may be beneficial against inflammatory diseases [10]. However, the research is still at a preliminary stage to date, which necessitates the need for further study.…”

Associations between healthy food groups and platelet-activating factor, lipoprotein-associated phospholipase A2 and C-reactive protein: a cross-sectional study

“…PAF is an ether-linked glycerophospholipid that is one of the most potent inflammatory mediators in the body that is active in nanomolar concentrations and is closely implicated in all stages of atherosclerosis [ 9 ]. PAF is produced by numerous cells such as platelets, endothelial cells, and leukocytes and triggers an inflammatory cascade through the act of binding to the G-protein coupled PAF receptor [ 10 , 11 ]. PAF is involved in the early stages of atherosclerosis by the mediation of adhesion of monocytes to the endothelium and increasing endothelial permeability, allowing low-density lipoproteins (LDL) and monocytes to migrate into the intima [ 12 , 13 ].…”