Platelet lipidome: Dismantling the “Trojan horse” in the bloodstream

Abstract

The platelet‐lipid chapter in the story of atherothrombosis is an old one, recapitulated and revised in many contexts. For decades several stimulating facets have been added to it, both unraveling and increasing the perplexity of platelet‐lipid interplay and its pathophysiological consequences. The recent paradigm shift in our perspective has evolved with lipidomic analysis of the intraplatelet compartment and platelet releasate. These investigations have disclosed that platelets are in constant interaction with circulatory lipids, often reflected in their lipid repertoire. In addition, they offer a shielded intracellular space for oxidative lipid metabolism generating “toxic” metabolites that escape degradation by plasma lipases and antioxidant defense, circulate undetected by conventional plasma lipid profile, and deposited at atherosclerotic lesions or thrombus. Lipidomics divulges this silent invader in platelet vehicles, thereby providing potential biomarkers of pathologic manifestations and therapeutic targets to be exploited, which is surmised in this review.

Platelet-derived lysophosphatidic acid mediated LPAR1 activation as a therapeutic target for osteosarcoma metastasis

“…Lipid mediators, such as TxA2, S1P, and LPA, have reportedly been produced and released upon platelet activation, as shown by the mass spectrometry analysis of lipids in platelet releasate [ 32 , 33 ]. We therefore compared the gene expression profiles of the receptors of these lipid mediators (TBA2R, S1PR1-5, and LPAR1-6) in osteosarcoma patient samples using RNA-seq data retrieved from the TARGET osteosarcoma project database.…”

Inflammation and Cardiovascular Disease: The Future

“…[ 72 ] Interestingly, the recent introduction of platelet lipidomics reemphasised the role of circulatory lipids in inflammation-driven thrombosis. [ 73 ] Several components of lipid metabolism, such as oxidised LDL and especially Lp(a), are thought to promote potent prothrombogenic activity. [ 12 , 56 , 61 ] Moreover, rosuvastatin might have an additional pleiotropic effect beyond its anti-inflammatory properties by reducing platelet membrane cholesterol, as well as by diminishing levels of tissue factor, factor VII and factor X.…”

Novel Approaches to Fine-Tune Therapeutic Targeting of Platelets in Atherosclerosis: A Critical Appraisal

“…56 Nevertheless, several prenols, saccharolipids, and polyketines have important functions in platelet biology and have been reviewed elsewhere. [57][58][59] Polyunsaturated Fatty Acids Are Regulators of Platelet Activity and Affect Atherosclerosis FAs can harbor multiple double bonds (PUFAs, polyunsaturated FAs). The position of the first double bond at the methyl end (omega, opposite the carboxyl group) explains the terminology so that omega-3 (n-3) FAs such as eicosapentaenoic acid (EPA) are differentiated from omega-6 FAs like arachidonic acid (AA).…”

“…While AA serves as a precursor for the potent platelet activator thromboxane A2 and an opponent of the potent platelet inhibitor PGI2 (prostacyclin), EPA can be metabolized in platelets to various inhibitory lipids like thromboxane A3. 59 These lipid mediators have a short half-life so that they are generated on demand. Adding AA to whole blood rapidly induces platelet activation in an autocrine manner via thromboxane binding to its G i -coupled receptor TP on platelets, whereas PGI2 is produced by endothelial cells and activates in a paracrine fashion its G s -coupled receptor IP.…”