Untargeted Metabolic Profiling of Extracellular Vesicles of SARS-CoV-2-Infected Patients Shows Presence of Potent Anti-Inflammatory Metabolites

Alzahrani, Faisal; Mohammed, Mohammed Razeeth Shait; Alkarim, Saleh; Azhar, Esam I.; El-Magd, Mohammed A.; Hawsawi, Yousef M.; Abdulaal, Wesam H.; Yusuf, Abdulaziz; Alhatmi, Abdulaziz; Albiheyri, Raed; Fakhurji, Burhan; Kurdi, Bassem; Madani, Tariq A.; Alguridi, Hassan; Alosaimi, Roaa S; Khan, Mohammad Imran

doi:10.3390/ijms221910467

Cited by 18 publications

(15 citation statements)

References 71 publications

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“…by regulating neutrophil recruitment to the lungs via CXCL8 or by binding of TLR4 to the viral spike protein ( Meidert et al, 2021 ). On the other hand, EVs may also contain anti-inflammatory metabolites, which are crucial in coping with overshooting inflammation ( Alzahrani et al, 2021 ).…”

Section: Roles Of Evs In Inflammation Cancer and Thrombosismentioning

confidence: 99%

Extracellular Vesicles Linking Inflammation, Cancer and Thrombotic Risks

Beck¹,

Hochreiter²,

Schmid³

2022

Front. Cell Dev. Biol.

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Extracellular vesicles (EVs) being defined as lipid-bilayer encircled particles are released by almost all known mammalian cell types and represent a heterogenous set of cell fragments that are found in the blood circulation and all other known body fluids. The current nomenclature distinguishes mainly three forms: microvesicles, which are formed by budding from the plasma membrane; exosomes, which are released, when endosomes with intraluminal vesicles fuse with the plasma membrane; and apoptotic bodies representing fragments of apoptotic cells. Their importance for a great variety of biological processes became increasingly evident in the last decade when it was discovered that they contribute to intercellular communication by transferring nucleotides and proteins to recipient cells. In this review, we delineate several aspects of their isolation, purification, and analysis; and discuss some pitfalls that have to be considered therein. Further on, we describe various cellular sources of EVs and explain with different examples, how they link cancer and inflammatory conditions with thrombotic processes. In particular, we elaborate on the roles of EVs in cancer-associated thrombosis and COVID-19, representing two important paradigms, where local pathological processes have systemic effects in the whole organism at least in part via EVs. Finally, we also discuss possible developments of the field in the future and how EVs might be used as biomarkers for diagnosis, and as vehicles for therapeutics.

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Section: Roles Of Evs In Inflammation Cancer and Thrombosismentioning

confidence: 99%

Extracellular Vesicles Linking Inflammation, Cancer and Thrombotic Risks

Beck¹,

Hochreiter²,

Schmid³

2022

Front. Cell Dev. Biol.

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“…Serum-derived EVs are essential not only for bipolar disorder research, 73 they also provide anti-inflammatory substances and antibiotics to COVID-19 patients, 74 as well as in Alzheimer’s disease. 50 , 75 Due to the complexity of whole blood substances, blood-derived EVs are rarely used.…”

Section: How Potential Of Metabolomics Of Extracellular Vesicles In C...mentioning

confidence: 99%

“… 106 In addition, anti-inflammatory molecules (LysoPS, 7-α, 25-dihydroxycholesterol and 15-d-PGJ2) and coagulation (thromboxane and ellagic acid) related metabolites in EVs may play critical roles in reducing inflammation of COVID-19. 74 EVs metabolomic analysis was also applied to monitor glioblastoma. 107 Surprisingly, the technique has been practiced to measure the surface lipid composition and viscosity of the nanoparticles, and evaluate intrauterine hypoxic injury of placental trophoblasts.…”

Section: What Is the Potential Of Metabolomics Of Extracellular Vesic...mentioning

confidence: 99%

Metabolomics of Extracellular Vesicles: A Future Promise of Multiple Clinical Applications

Wu¹,

Chen²,

Guo³

et al. 2022

IJN

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Extracellular vesicles (EVs) can contain DNA, RNA, proteins and metabolic molecules from primary origins; they are coated with a phospholipid bilayer membrane and released by cells into the extracellular matrix. EVs can be obtained from various body liquids, including the blood, saliva, cerebrospinal fluid, and urine. As has been proved, EVs-mediated transfer of biologically active molecules is crucial for various physiological and pathological processes. Extensive investigations have already begun to explore the diagnosis and prognosis potentials for EVs. Furthermore, research has continued to recognize the critical role of nucleic acids and proteins in EVs. However, our understanding of the comprehensive effects of metabolites in these nanoparticles is currently limited and in its infancy. Therefore, we have attempted to summarize the recent research into the metabolomics of EVs in relation to potential clinical applications and discuss the problems and challenges that have occurred, to provide more guidance for the future development in this field.

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“…An exciting area for research is the role of exosomes in healthy and pathological pregnancies. In inflammatory pathologies, such as SARS-CoV-2, diabetic nephropathy or even GDM, exosome have represented important biological tools in identifying specific molecular content as critical regulators of inflammation, such as drug and anti-inflammatory metabolites, or microRNAs [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Exosome Proteomics Reveals the Deregulation of Coagulation, Complement and Lipid Metabolism Proteins in Gestational Diabetes Mellitus

Bernea¹,

Suica²,

Uyy³

et al. 2022

Molecules

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Exosomes are small extracellular vesicles with a variable protein cargo in consonance with cell origin and pathophysiological conditions. Gestational diabetes mellitus (GDM) is characterized by different levels of chronic low-grade inflammation and vascular dysfunction; however, there are few data characterizing the serum exosomal protein cargo of GDM patients and associated signaling pathways. Eighteen pregnant women were enrolled in the study: 8 controls (CG) and 10 patients with GDM. Blood samples were collected from patients, for exosomes’ concentration. Protein abundance alterations were demonstrated by relative mass spectrometric analysis and their association with clinical parameters in GDM patients was performed using Pearson’s correlation analysis. The proteomics analysis revealed 78 significantly altered proteins when comparing GDM to CG, related to complement and coagulation cascades, platelet activation, prothrombotic factors and cholesterol metabolism. Down-regulation of Complement C3 (C3), Complement C5 (C5), C4-B (C4B), C4b-binding protein beta chain (C4BPB) and C4b-binding protein alpha chain (C4BPA), and up-regulation of C7, C9 and F12 were found in GDM. Our data indicated significant correlations between factors involved in the pathogenesis of GDM and clinical parameters that may improve the understanding of GDM pathophysiology. Data are available via ProteomeXchange with identifier PXD035673.

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Untargeted Metabolic Profiling of Extracellular Vesicles of SARS-CoV-2-Infected Patients Shows Presence of Potent Anti-Inflammatory Metabolites

Cited by 18 publications

References 71 publications

Extracellular Vesicles Linking Inflammation, Cancer and Thrombotic Risks

Extracellular Vesicles Linking Inflammation, Cancer and Thrombotic Risks

Metabolomics of Extracellular Vesicles: A Future Promise of Multiple Clinical Applications

Exosome Proteomics Reveals the Deregulation of Coagulation, Complement and Lipid Metabolism Proteins in Gestational Diabetes Mellitus

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