Alterations in platelet proteome signature and impaired platelet integrin αIIbβ3 activation in patients with COVID-19

Goudswaard, Lucy J; Williams, Christopher; Khalil, Jawad S.; Burley, K; Hamilton, Fergus; Arnold, David; Milne, Alice; Lewis, Phil A.; Heesom, Kate J; Mundell, Stuart J.; Davidson, Andrew D.; Poole, Alastair W.; Hers, Ingeborg

doi:10.1016/j.jtha.2023.01.018

Cited by 8 publications

(7 citation statements)

References 71 publications

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“…The three acute-phase proteins have already been associated with a predictive function for COVID-19 in various plasma proteome studies [40,41]. CRP and SAA are plasma proteins that, to the best of our knowledge, have only been detected in platelets in a proteomic analysis of platelets from COVID-19 platelets [21] but not in any other context. So far, there is no evidence of endocytosis in CRP or SAA or of increased transcription in the situation of COVID-19 [16].…”

Section: Discussionmentioning

confidence: 92%

“…Analyses of the platelet proteome have been performed for various diseases of bacterial and viral origin and have revealed specific changes in platelet protein compositions [45,46]. Alterations in the platelet proteome have also been observed in SARS-CoV-2 infections [20][21][22]. Platelet involvement in COVID-19 seems to play a role in the most affected patients.…”

Section: Discussionmentioning

confidence: 99%

“…Manne et al found changes in the transcriptome of such platelets related to protein ubiquitinylation, mitochondrial dysfunction, and antigen presentation [16]. Proteomic studies revealed significant changes in the expression of proteins related to cell death and antiviral response [17], as well as platelet activation and granule secretion [20,21]. In addition, increased levels of protein disulfide isomerases, among others, were found in platelets from COVID-19 patients [22].…”

Section: Introductionmentioning

confidence: 99%

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Changes in the Proteome of Platelets from Patients with Critical Progression of COVID-19

Wolny,

Rozanova,

Knabbe

et al. 2023

Cells

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Platelets, the smallest cells in human blood, known for their role in primary hemostasis, are also able to interact with pathogens and play a crucial role in the immune response. In severe coronavirus disease 2019 (COVID-19) cases, platelets become overactivated, resulting in the release of granules, exacerbating inflammation and contributing to the cytokine storm. This study aims to further elucidate the role of platelets in COVID-19 progression and to identify predictive biomarkers for disease outcomes. A comparative proteome analysis of highly purified platelets from critically diseased COVID-19 patients with different outcomes (survivors and non-survivors) and age- and sex-matched controls was performed. Platelets from critically diseased COVID-19 patients exhibited significant changes in the levels of proteins associated with protein folding. In addition, a number of proteins with isomerase activity were found to be more highly abundant in patient samples, apparently exerting an influence on platelet activity via the non-genomic properties of the glucocorticoid receptor (GR) and the nuclear factor κ-light-chain-enhancer of activated B cells (NFκB). Moreover, carbonic anhydrase 1 (CA-1) was found to be a candidate biomarker in platelets, showing a significant increase in COVID-19 patients.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Changes in the Proteome of Platelets from Patients with Critical Progression of COVID-19

Wolny,

Rozanova,

Knabbe

et al. 2023

Cells

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“…Recent studies found impaired integrin activity in platelet of COVID-19 patients versus healthy controls, with a more pronounced decline of integrin alpha IIb in severe COVID-19 patients. 28,29 Additionally, thrombocytopenia in COVID-19 was found to have a varying incidence of 23% to 36%, with increasing incidence in more severe cases, possibly as a result of a hypercoagulative state before endstage COVID-19. [30][31][32] A similar phenomenon regarding certain cytokine signalling pathways may also occur.…”

Section: Discussionmentioning

confidence: 99%

Increase in venous thromboembolism in SARS‐CoV‐2 infected lung tissue: proteome analysis of lung parenchyma, isolated endothelium, and thrombi

Lopuhaä,

Guzel,

van der Lee

et al. 2024

Histopathology

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AimsCOVID‐19 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID‐19, we performed proteomics analysis on SARS‐CoV‐2 infected lung tissue.MethodsLiquid chromatography mass spectrometry was performed on SARS‐CoV‐2 infected postmortem lung tissue samples. Five protein profiling analyses were performed: whole slide lung parenchyma analysis, followed by analysis of isolated thrombi and endothelium, both stratified by disease (COVID‐19 versus influenza) and thrombus morphology (embolism versus in situ). Influenza autopsy cases with pulmonary thrombi were used as controls.ResultsCompared to influenza controls, both analyses of COVID‐19 whole‐tissue and isolated endothelium showed upregulation of proteins and pathways related to liver metabolism including urea cycle activation, with arginase being among the top upregulated proteins in COVID‐19 lung tissue. Analysis of isolated COVID‐19 thrombi showed significant downregulation of pathways related to platelet activation compared to influenza thrombi. Analysis of isolated thrombi based on histomorphology shows that in situ thrombi have significant upregulation of coronavirus pathogenesis proteins.ConclusionsThe decrease in platelet activation pathways in severe COVID‐19 thrombi suggests a relative increase in venous thromboembolism, as thrombi from venous origin tend to contain fewer platelets than arterial thrombi. Based on histomorphology, in situ thrombi show upregulation of various proteins related to SARS‐CoV‐2 pathogenesis compared to thromboemboli, which may indicate increased in situ pulmonary thrombosis in COVID‐19. Therefore, this study supports the increase of venous thromboembolism without undercutting the involvement of in situ thrombosis in severe COVID‐19.

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“…Platelets were isolated as described previously [30]. Briefly blood from healthy drug-free volunteers was drawn into 3.2% (w/v) trisodium citrate according to local NHS research ethics approval (20/SC/0222) and the Declaration of Helsinki.…”

Section: Author Contributionsmentioning

confidence: 99%

CryoET reveals actin filaments within platelet microtubules

Tsuji,

Bradshaw,

Allen

et al. 2023

Preprint

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Crosstalk between the actin and microtubule cytoskeletons is essential for many cellular processes. Recent studies have shown that microtubules and F-actin can assemble to form a composite structure where F-actin occupies the microtubule lumen. Whether these cytoskeletal hybrids exist in physiological settings and how they are formed is unclear. Here, we show that the short-crossover Class I actin filament previously identified inside microtubules in human HAP1 cells is cofilin-bound F-actin. Lumenal F-actin can be reconstitutedin vitro, but cofilin is not essential. Moreover, actin filaments with both cofilin-bound and canonical morphologies reside within human platelet microtubules under physiological conditions. We propose that stress placed upon the microtubule network during motor-driven microtubule looping and sliding may facilitate the incorporation of actin into microtubules.

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Alterations in platelet proteome signature and impaired platelet integrin αIIbβ3 activation in patients with COVID-19

Cited by 8 publications

References 71 publications

Changes in the Proteome of Platelets from Patients with Critical Progression of COVID-19

Changes in the Proteome of Platelets from Patients with Critical Progression of COVID-19

Increase in venous thromboembolism in SARS‐CoV‐2 infected lung tissue: proteome analysis of lung parenchyma, isolated endothelium, and thrombi

CryoET reveals actin filaments within platelet microtubules

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