Anti-GPVI Fab reveals distinct roles for GPVI signaling in the first platelet layer and subsequent layers during microfluidic clotting on collagen with or without tissue factor

Zhang, Y.; Trigani, Kevin T.; Shankar, Kaushik Nagaraj; Crossen, J.; Liu, Yi‐Jun; Sinno, Talid; Diamond, Scott L.

doi:10.1016/j.thromres.2022.08.018

Cited by 6 publications

(5 citation statements)

References 43 publications

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“…Other studies employing Fab blockade of GPVI have demonstrated similar results, highlighting the importance of GPVI-fibrin interactions in maintaining thrombus integrity during the early stages of thrombosis. 28 Interestingly, we found no difference in GPVI expression between anticoagulated and nonanticoagulated AF patients (►Supplementary Fig. S1), a finding consistent with previous published research.…”

Section: Discussionsupporting

confidence: 92%

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Platelet Receptor Glycoprotein VI-Dimer Is Overexpressed in Patients with Atrial Fibrillation at High Risk of Ischemic Stroke

Induruwa,

Kempster,

Thomas

et al. 2023

TH Open

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Introduction Atrial fibrillation (AF) increases the risk of ischemic stroke (IS). We hypothesized that the functional form of platelet receptor glycoprotein (GP) VI, GPVI-dimer, which binds to collagen and fibrin causing platelet activation, is overexpressed in patients with AF who have not had a stroke. Methods A total of 75 inpatients with AF were recruited. None were admitted with or had previously had thrombotic events, including IS or myocardial infarction. Platelet surface expression of total GPVI, GPVI-dimer, and the platelet activation marker P-selectin were quantitated by whole blood flow cytometry. Serum biomarkers were collected in AF patients. Results were compared against patients contemporaneously admitted to hospital with similar age and vascular risk-factor profiles without AF (noAF, n = 30). Results Patients with AF have similar total GPVI surface expression (p = 0.58) and P-selectin exposure (p = 0.73) on their platelets compared with noAF patients but demonstrate significantly higher GPVI-dimer expression (p = 0.02). Patients with paroxysmal AF express similar GPVI-dimer levels compared with permanent AF and GPVI-dimer levels were not different between anticoagulated groups. Serum N-terminal pro b-type natriuretic peptide (p < 0.0001) and high sensitivity C-reactive protein (p < 0.0001) were significantly correlated with GPVI-dimer expression in AF platelets. AF was the only vascular risk factor that was independently associated with higher GPVI-dimer expression in the whole population (p = 0.02). Conclusion GPVI inhibition is being explored in clinical trials as a novel target for IS treatment. As GPVI-dimer is elevated in AF patients' platelets, the exploration of targeted GPVI-dimer inhibition for stroke prevention in patients at high risk of IS due to AF is supported.

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Section: Discussionsupporting

confidence: 92%

“…Other studies employing Fab blockade of GPVI have demonstrated similar results, highlighting the importance of GPVI–fibrin interactions in maintaining thrombus integrity during the early stages of thrombosis. 28 …”

Section: Discussionmentioning

confidence: 99%

Platelet Receptor Glycoprotein VI-Dimer Is Overexpressed in Patients with Atrial Fibrillation at High Risk of Ischemic Stroke

Induruwa,

Kempster,

Thomas

et al. 2023

TH Open

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“…37 Thrombogenic agents such as collagen, TFs, fibrin, fibrinogen, and VWF are usually incorporated in microchannels to initiate clot formation. 17,87 Choi et al, 17 for instance, used a collagen-coated PDMS channel with circular cross-section and showed thrombus growth process in an 83.73% stenosis region (Figure 2G). The channels can be coated with collagen and TF patch to simulate plaque rupture and platelet activation, allowing for determination of time to occlude and investigation of antiplatelet drug effects.…”

Section: Examples Of Vascular Disease Modeling-on-a-chip Atherosclero...mentioning

confidence: 98%

“…22,41,42,85,90 Furthermore, cells and media retrieved from the device enable further investigations such as RNA sequencing, secretomics, and metabolomics 16,20,78 Snapshot Imaging Snapshot imaging in OOC systems corresponds to capturing a single moment in time for in-depth analysis. 16,18,37,39,51,62,78,86,87 These observations provide valuable insights into disease events, helping identify rapid changes in vascular cell behavior in response to specific stimuli. Snapshot imaging typically occurs after cell fixation, where cells are chemically preserved at a specific moment.…”

Section: Characterization Of Vascular Models-on-a-chipmentioning

confidence: 99%

“…36 Coaxial 3D printing of 2-layered hydrogels was used for bioprinting of vein-and artery-like conduits. 34 Thrombosis Stenosis-integrated channel, 17,19,37,58,64,84,85 continues channel, 22,[86][87][88][89][90] H-shaped channel, 91 T-shaped channel, 92,93 Y-shaped channel, 20,42,94 branching channels 35,37,95 PDMS/glass, [19][20][21][22]58,64,86,87,91,96 PDMS, 17,84,88,92 glass, 85 GelMA, 42 collagen, 37 PDMS/ silica, 95 commercial devices, 89,90 agarose/gelatin 35 HUVECs, HDMVECs, HLMVECs, collagen, collagen/TF, VWF, fibroblasts, fibronectin…”

Section: Long-term Observationmentioning

confidence: 99%

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Engineering Organ-on-a-Chip Systems for Vascular Diseases

Shakeri,

Wang,

Zhao

et al. 2023

ATVB

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Vascular diseases, such as atherosclerosis and thrombosis, are major causes of morbidity and mortality worldwide. Traditional in vitro models for studying vascular diseases have limitations, as they do not fully recapitulate the complexity of the in vivo microenvironment. Organ-on-a-chip systems have emerged as a promising approach for modeling vascular diseases by incorporating multiple cell types, mechanical and biochemical cues, and fluid flow in a microscale platform. This review provides an overview of recent advancements in engineering organ-on-a-chip systems for modeling vascular diseases, including the use of microfluidic channels, ECM (extracellular matrix) scaffolds, and patient-specific cells. We also discuss the limitations and future perspectives of organ-on-a-chip for modeling vascular diseases.

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Investigating thrombin-loaded fibrin in whole blood clot microfluidic assay via fluorogenic peptide

Crossen

Shankar

Diamond

2023

Biophysical Journal

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Anti-GPVI Fab reveals distinct roles for GPVI signaling in the first platelet layer and subsequent layers during microfluidic clotting on collagen with or without tissue factor

Cited by 6 publications

References 43 publications

Platelet Receptor Glycoprotein VI-Dimer Is Overexpressed in Patients with Atrial Fibrillation at High Risk of Ischemic Stroke

Platelet Receptor Glycoprotein VI-Dimer Is Overexpressed in Patients with Atrial Fibrillation at High Risk of Ischemic Stroke

Engineering Organ-on-a-Chip Systems for Vascular Diseases

Investigating thrombin-loaded fibrin in whole blood clot microfluidic assay via fluorogenic peptide

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