Relative survival potential of platelets is associated with platelet CXCR4/CXCR7 surface exposure and functional recovery following STEMI

Rath, Dominik; Chatterjee, Mainak; Meyer, Lennart; Tekath, Nina; Olma, Carolin; Krumm, Patrick; Adams, Constantin; Müller, Karin; Droppa, Michal; Nikolaou, Konstantin; Riethmüller, Joachim; Gawaz, Meinrad; Geisler, Tobias

doi:10.1016/j.atherosclerosis.2018.10.008

Cited by 19 publications

(24 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Detection of PS externalization PRP was stained with Annexin V-fluorescein isothiocyanate (Immunotools, Friesoyhte, Germany) and CD41-PE-Cy5 (Beckman Coulter) in TRIS buffer (30 minutes at room temperature) and directly analyzed by FC, as previously described. 25 Cells incubated with 60 mM ionomycin (30 minutes at room temperature) served as a positive control. Test results were determined as fold increase of the percentage of PS-positive events in PRP from COVID-19 or non-COVID-19 patients in the ICU compared with platelets from healthy donors tested in parallel.…”

Section: Assessment Of the Inner Dcmmentioning

confidence: 99%

Antibody-induced procoagulant platelets in severe COVID-19 infection

Althaus

Marini

Zlamal

et al. 2021

Blood

Self Cite

182

178

View full text Add to dashboard Cite

The pathophysiology of COVID-19 associated thrombosis seems to be multifactorial. We hypothesized that COVID-19 is accompanied by procoagulant platelets and platelet apoptosis with subsequent alteration of the coagulation system. We investigated depolarization of mitochondrial inner transmembrane potential (ΔΨm), cytosolic calcium (Ca2+) concentration, and phosphatidylserine (PS) externalization by flow cytometry. Platelets from intensive care unit (ICU) COVID-19 patients (n=21) showed higher ΔΨm depolarization, cytosolic Ca2+ concentration and PS externalization, compared to healthy controls (n=18) and COVID-19 non-ICU patients (n=4). Moreover significant higher cytosolic Ca2+ concentration and PS was observed compared to septic ICU control group (ICU control). In ICU control group (n=5; ICU non-COVID-19) cytosolic Ca2+ concentration and PS externalization was comparable to healthy control, with an increase in ΔΨm depolarization. Sera from ICU COVID-19 patients induced significant increase in apoptosis markers (ΔΨm depolarization, cytosolic Ca2+ concentration and PS externalization) compared to healthy volunteer and septic ICU control. Interestingly, immunoglobulin G (IgG) fractions from COVID-19 patients induced an Fc gamma receptor IIA dependent platelet apoptosis (ΔΨm depolarization, cytosolic Ca2+ concentration and PS externalization). Enhanced PS externalization in platelets from ICU COVID-19 patients was associated with increased sequential organ failure assessment (SOFA) score (r=0.5635) and D-Dimer (r=0.4473). Most importantly, patients with thrombosis had significantly higher PS externalization compared to those without. The strong correlations between procoagulant platelet and apoptosis markers and increased D-Dimer levels as well as the incidence of thrombosis may indicate that antibody-mediated platelet apoptosis potentially contributes to sustained increased thromboembolic risk in ICU COVID-19 patients.

show abstract

Section: Assessment Of the Inner Dcmmentioning

confidence: 99%

Antibody-induced procoagulant platelets in severe COVID-19 infection

Althaus

Marini

Zlamal

et al. 2021

Blood

Self Cite

182

178

View full text Add to dashboard Cite

show abstract

“…PRP was stained with Annexin V-FITC (Immunotools, Friesoyhte Germany) and CD41-PE-Cy5 (Beckman Coulter, Brea, USA) in TRIS buffer (30 min* at RT) and directly analyzed by FC, as previously described 25 . Cells incubated with 60 μM ionomycin (30 min* at RT) served as positive control.…”

Section: Methodsmentioning

confidence: 99%

Severe COVID-19 infection is associated with increased antibody-mediated platelet apoptosis

Althaus

Marini

Zlamal

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

The pathophysiology of COVID-19 associated thrombosis seems to be multifactorial, involving interplay between cellular and plasmatic elements of the hemostasis. We hypothesized that COVID-19 is accompanied by platelet apoptosis with subsequent alteration of the coagulation system. We investigated depolarization of mitochondrial inner transmembrane potential (ΔΨm), cytosolic calcium (Ca2+) concentration, and phosphatidylserine (PS) externalization by flow cytometry. Platelets from intensive care unit (ICU) COVID-19 patients (n=21) showed higher ΔΨm depolarization, cytosolic Ca2+ concentration and PS externalization, compared to healthy controls (n=18) and COVID-19 non-ICU patients (n=4). Moreover significant higher cytosolic Ca2+ concentration and PS was observed compared to septic ICU control group (ICU control). In ICU control group (n=5; non-COVID-19 ICU) cytosolic Ca2+ concentration and PS externalization was comparable to healthy control, with an increase in ΔΨm depolarization. Sera from ICU COVID-19 patients induced significant increase in apoptosis markers (ΔΨm depolarization, cytosolic Ca2+ concentration and PS externalization) compared to healthy volunteer and septic ICU control. Interestingly, immunoglobulin G (IgG) fractions from COVID-19 patients induced an Fc gamma receptor IIA dependent platelet apoptosis (ΔΨm depolarization, cytosolic Ca2+ concentration and PS externalization). Enhanced PS externalization in platelets from ICU COVID-19 patients was associated with increased sequential organ failure assessment (SOFA) score (r=0.5635) and D-Dimer (r=0.4473). Most importantly, patients with thrombosis had significantly higher PS externalization compared to those without. The strong correlations between apoptosis markers and increased D-Dimer levels as well as the incidence of thrombosis may indicate that antibody-mediated platelet apoptosis potentially contributes to sustained increased thromboembolic risk in ICU COVID-19 patients.

show abstract

“…Circulatory levels of CXCL12/SDF1α [ 38 , 44 ] and MIF [ 45 ] are elevated in ACS patients and are furthermore associated with progressive disease severity. Therefore, CXCL12/SDF1α and MIF in circulation may influence the relative surface expression and involvement of CXCR4-ACKR3/CXCR7 in modulating platelet response and survival potential [ 24 ]. Although both CXCR4 and ACKR3/CXCR7 serve as cognate receptors for CXCL12/SDF-1α and MIF, they are involved in quite contrasting functional responses, as discussed next [ 21 ].…”

Section: The Dichotomy Of Cxcr4 and Ackr3/cxcr7 In Plateletsmentioning

confidence: 99%

“…It also correlates with platelet surface-associated CXCL12/SDF1α [ 23 ]. Moreover, platelet ACKR3/CXCR7 surface expression ascertained upon admission immediately following an acute thrombo-ischemic event, is associated with significantly improved functional recovery (LVEF) and prognosis [ 23 , 24 ], evaluated during a hospital stay of 5 days, and over a 6 month follow-up period. The prognostic significance of platelet CXCR4 surface expression at baseline, which though comparable between stable CAD and ACS patients becomes more prominent after a 1-year follow up.…”

Section: Introductionmentioning

confidence: 99%

Atypical Roles of the Chemokine Receptor ACKR3/CXCR7 in Platelet Pathophysiology

Chatterjee

2022

Cells

Self Cite

View full text Add to dashboard Cite

The manifold actions of the pro-inflammatory and regenerative chemokine CXCL12/SDF-1α are executed through the canonical GProteinCoupledReceptor CXCR4, and the non-canonical ACKR3/CXCR7. Platelets express CXCR4, ACKR3/CXCR7, and are a vital source of CXCL12/SDF-1α themselves. In recent years, a regulatory impact of the CXCL12-CXCR4-CXCR7 axis on platelet biogenesis, i.e., megakaryopoiesis, thrombotic and thrombo-inflammatory actions have been revealed through experimental and clinical studies. Platelet surface expression of ACKR3/CXCR7 is significantly enhanced following myocardial infarction (MI) in acute coronary syndrome (ACS) patients, and is also associated with improved functional recovery and prognosis. The therapeutic implications of ACKR3/CXCR7 in myocardial regeneration and improved recovery following an ischemic episode, are well documented. Cardiomyocytes, cardiac-fibroblasts, endothelial lining of the blood vessels perfusing the heart, besides infiltrating platelets and monocytes, all express ACKR3/CXCR7. This review recapitulates ligand induced differential trafficking of platelet CXCR4-ACKR3/CXCR7 affecting their surface availability, and in regulating thrombo-inflammatory platelet functions and survival through CXCR4 or ACKR3/CXCR7. It emphasizes the pro-thrombotic influence of CXCL12/SDF-1α exerted through CXCR4, as opposed to the anti-thrombotic impact of ACKR3/CXCR7. Offering an innovative translational perspective, this review also discusses the advantages and challenges of utilizing ACKR3/CXCR7 as a potential anti-thrombotic strategy in platelet-associated cardiovascular disorders, particularly in coronary artery disease (CAD) patients post-MI.

show abstract

Relative survival potential of platelets is associated with platelet CXCR4/CXCR7 surface exposure and functional recovery following STEMI

Cited by 19 publications

References 37 publications

Antibody-induced procoagulant platelets in severe COVID-19 infection

Antibody-induced procoagulant platelets in severe COVID-19 infection

Severe COVID-19 infection is associated with increased antibody-mediated platelet apoptosis

Atypical Roles of the Chemokine Receptor ACKR3/CXCR7 in Platelet Pathophysiology

Contact Info

Product

Resources

About