Platelet Lipidomics

Abstract

Lipids are diverse families of biomolecules that perform essential structural and signaling roles in platelets. Their formation and metabolism is tightly controlled by enzymes and signal transduction pathways, and their dysregulation leads to significant defects in platelet function and disease. Platelet activation is associated with significant changes to membrane lipids, and formation of diverse bioactive lipids that play essential roles in hemostasis. In recent years, new generation mass spectrometry analysis of lipids (termed “lipidomics”) has begun to alter our understanding of how these molecules participate in key cellular processes. While, the application of lipidomics to platelet biology is still in its infancy, seminal earlier studies have shaped our knowledge of how lipids regulate key aspects of platelet biology, including aggregation, shape change, coagulation and degranulation, as well as how lipids generated by platelets influence other cells, such as leukocytes and the vascular wall, and thus how they regulate hemostasis, vascular integrity and inflammation, as well as contribute to pathologies including arterial/deep vein thrombosis and atherosclerosis. This review will provide a brief historical perspective on the characterization of lipids in platelets, then an overview of the new generation lipidomic approaches, their recent application to platelet biology, and future perspectives for research in this area. The major platelet-regulatory lipid families, their formation, metabolism, and their role in health and disease, will be summarized.

Aspirin inhibits the production of proangiogenic 15(S)‐HETE by platelet cyclooxygenase‐1

“…We conducted incubations under stirring conditions because this better predicts platelet reactivity in the body than static conditions (17). As others and we have reported previously (9, 18, 19), activated platelets produce a broad range of AA-derived eicosanoids. Notably, in our studies we found 11-HETE and 15-HETE to be major products formed at similar levels to TXA 2 through the action of group IV A cytosolic phospholipase A 2 and COX-1.…”

Oleocanthal-rich extra virgin olive oil demonstrates acute anti-platelet effects in healthy men in a randomized trial

“…Therapeutic reduction of cardiovascular disease progression and events has focused on limiting platelet activation through inhibition of cyclooxygenase (COX), phosphodiesterase, adenosine diphosphate (ADP) receptors, and platelet-platelet interactions through glycoprotein IIb/IIIa (Yousuf & Bhatt, 2011). Major lipid remodelling occurs upon platelet activation that includes shape change, degranulation and generation of a number of bioactive species that amplify activation while promoting clot stabilization and inflammation (O’Donnell, Murphy, & Watson, 2014). Oxylipins are a superclass of bioactive lipids produced from polyunsaturated fatty acid oxidation.…”

A MALDI-MSI Approach to the Characterization of Radiation-Induced Lung Injury and Medical Countermeasure Development

“…Advancements in analytical technology and instrumentation have enabled more robust and sensitive methods for detection and identification of these small molecules, leading to a greater understanding of their involvement in disease pathology(Schmelzer et al 2007, Loizides-Mangold 2013, O’Donnell et al 2014). First coined a little over a decade ago, lipidomics is defined as the analysis of lipids in a given system, their molecular functions, and their interacting molecules(Kishimoto et al 2001, Loizides-Mangold 2013).…”