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

Rajendran Harishkumar, Sakshi Hans, Janelle E Stanton, Andreas M Grabrucker, Ronan Lordan, Ioannis Zabetakis

Journal: Nutrients 2022;14(20):4414

PMID: 36297097

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.

Address: Department of Biological Sciences, University of Limerick, V94 T9PX Limerick, Ireland.; Bernal Institute, University of Limerick, V94 T9PX Limerick, Ireland.; Health Research Institute, University of Limerick, V94 T9PX Limerick, Ireland.; Cellular Neurobiology and Neuro-Nanotechnology Laboratory, Department of Biological Sciences, University of Limerick, V94 T9PX Limerick, Ireland.; Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Systems Pharmacology and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
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