A platelet lipidomics signature in patients with COVID-19

Goracci, Laura; Petito, Eleonora; Veroli, Alessandra Di; Falcinelli, Emanuela; Bencivenga, Caterina; Giglio, Elisa; Becattini, Cecilia; Robertis, Edoardo De; Vaudo, Gaetano; Gresele, Paolo

doi:10.1080/09537104.2023.2200847

Cited by 8 publications

(3 citation statements)

References 40 publications

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“…In the future, it would be of interest to investigate how CD36 signaling participate in these series of immune responses. Furthermore, studies have shown that COVID-19 patients may experience changes in blood lipid levels, including increased levels of triglycerides and low-density lipoprotein cholesterol (LDL-C) 44 , 45 , and dysregulated platelet lipid metabolism plays a role in the occurrence of thrombotic complications in COVID-19 46 . Considering that CD36 is a key receptor molecule involved in the cellular regulation of lipid influx, future studies are warranted to explore the role of E protein in the regulation of platelet lipid metabolism 38 , 40 .…”

Section: Discussionmentioning

confidence: 99%

CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis

Tang,

Xu,

Tan

et al. 2023

Nat Commun

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Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and mediates hyperactivation of human and mouse platelets through the p38 MAPK-NF-κB signaling pathway. Conversely, the pharmacological blockade of CD36 or p38 notably attenuates human platelet activation induced by the E protein. Similarly, the genetic deficiency of CD36, as well as the pharmacological inhibition of p38 in mice, significantly diminishes E protein-induced platelet activation and thrombotic events. Together, our study reveals a critical role for the CD36-p38 axis in E protein-induced platelet hyperactivity, which could serve as an actionable target for developing therapies against aberrant thrombotic events related to the severity and mortality of COVID-19.

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Section: Discussionmentioning

confidence: 99%

CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis

Tang,

Xu,

Tan

et al. 2023

Nat Commun

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“…On the other hand, Owens et al have already demonstrated that hyperlipidemic patients display high cholesterol amounts in platelet membranes [ 102 ]. Recently, it was demonstrated that the lipidomic signature of platelets from COVID-19 patients is different to that in healthy controls, with increased levels of ganglioside GM3 possibly related to the prothrombotic complications of the disease [ 103 ]. Therefore, the results cited above show how the multi-omics approach to analyzing platelets can provide a complete picture of their content and biology, helping to identify new markers that can be employed as prognostic or therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Platelet Metabolic Flexibility: A Matter of Substrate and Location

Ravera

Signorello

Panfoli

2023

Cells

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Platelets are cellular elements that are physiologically involved in hemostasis, inflammation, thrombotic events, and various human diseases. There is a link between the activation of platelets and their metabolism. Platelets possess considerable metabolic versatility. Although the role of platelets in hemostasis and inflammation is known, our current understanding of platelet metabolism in terms of substrate preference is limited. Platelet activation triggers an oxidative metabolism increase to sustain energy requirements better than aerobic glycolysis alone. In addition, platelets possess extra-mitochondrial oxidative phosphorylation, which could be one of the sources of chemical energy required for platelet activation. This review aims to provide an overview of flexible platelet metabolism, focusing on the role of metabolic compartmentalization in substrate preference, since the metabolic flexibility of stimulated platelets could depend on subcellular localization and functional timing. Thus, developing a detailed understanding of the link between platelet activation and metabolic changes is crucial for improving human health.

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“…15 Interestingly, a unique lipidomic signature has also been detected in platelets obtained from patients with coronavirus disease 2019, who are considered at heightened thrombotic risk. 16,17 Furthermore, statins can effectively mitigate platelet hyperreactivity by modulating intraplatelet lipid metabolism in individuals with ACS, thereby reducing the risk of thrombosis. 18 Therefore, regulation of intraplatelet lipid homeostasis may be a potential therapeutic target for minimizing the risk of thrombotic events.…”

mentioning

confidence: 99%

Glycoursodeoxycholic Acid Alleviates Arterial Thrombosis via Suppressing Diacylglycerol Kinases Activity in Platelet

Yang,

Feng,

Peng

et al. 2024

ATVB

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BACKGROUND: Glycoursodeoxycholic acid (GUDCA) has been acknowledged for its ability to regulate lipid homeostasis and provide benefits for various metabolic disorders. However, the impact of GUDCA on arterial thrombotic events remains unexplored. The objective of this study is to examine the effects of GUDCA on thrombogenesis and elucidate its underlying mechanisms. METHODS: Plasma samples from patients with arterial thrombotic events and diet-induced obese mice were collected to determine the GUDCA concentrations using mass spectrometry. Multiple in vivo murine thrombosis models and in vitro platelet functional assays were conducted to comprehensively evaluate the antithrombotic effects of GUDCA. Moreover, lipidomic analysis was performed to identify the alterations of intraplatelet lipid components following GUDCA treatment. RESULTS: Plasma GUDCA level was significantly decreased in patients with arterial thrombotic events and negatively correlated with thrombotic propensity in diet-induced obese mice. GUDCA exhibited prominent suppressing effects on platelet reactivity as evidenced by the attenuation of platelet activation, secretion, aggregation, spreading, and retraction ( P <0.05). In vivo, GUDCA administration robustly alleviated thrombogenesis ( P <0.05) without affecting hemostasis. Mechanistically, GUDCA inhibited DGK (diacylglycerol kinase) activity, leading to the downregulation of the phosphatidic acid–mediated signaling pathway. Conversely, phosphatidic acid supplementation was sufficient to abolish the antithrombotic effects of GUDCA. More importantly, long-term oral administration of GUDCA normalized the enhanced DGK activity, thereby remarkably alleviating the platelet hyperreactivity as well as the heightened thrombotic tendency in diet-induced obese mice ( P <0.05). CONCLUSIONS: Our study implicated that GUDCA reduces platelet hyperreactivity and improves thrombotic propensity by inhibiting DGKs activity, which is a potentially effective prophylactic approach and promising therapeutic agent for arterial thrombotic events.

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A platelet lipidomics signature in patients with COVID-19

Cited by 8 publications

References 40 publications

CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis

CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis

Platelet Metabolic Flexibility: A Matter of Substrate and Location

Glycoursodeoxycholic Acid Alleviates Arterial Thrombosis via Suppressing Diacylglycerol Kinases Activity in Platelet

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