Localization and Translocation of MMP-2 during Aggregation of Human Platelets

Sawicki, Grzegorz; Sanders, Esmond J.; Salas, Eduardo; Woźniak, Mieczysław; Rodrigo, José; Radomski, Marek W.

doi:10.1055/s-0037-1615367

Cited by 104 publications

(125 citation statements)

References 19 publications

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Section: Introductionmentioning

confidence: 99%

“…MMP-1 17 and MMP-2 18-20 were shown to prime platelets for adhesion and aggregation, whereas MMP-9 inhibited platelet activation. 19,20 However, a possible role of MMPs in PSL or the related cleavage of GPIb␣ has not yet been investigated.In this study, we show that specific mitochondrial damage induces morphologic and functional changes in platelets that resemble those of PSL. We further demonstrate that inhibition of platelet-derived metalloproteinase(s) during platelet in vitro aging or mitochondrial damage markedly improves the recovery of these …”

mentioning

confidence: 99%

“…Activation requires translocation to the cell surface and proteolytic cleavage of the proenzyme. 17,20,46 Experiments directed at identifying the metalloproteinase(s) involved in the clearance of damaged platelets are in progress. Our data point to the possibility that cleavage of GPIb␣ may play a role in the clearance of damaged platelets.…”

mentioning

confidence: 99%

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Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro–aged or –injured mouse platelets

Bergmeier

Burger

Piffath

et al. 2003

Blood

159

178

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Platelet transfusions are a crucial component of support for patients with severe thrombocytopenia. Storage of platelet concentrates, however, is associated with a reduction in platelet posttransfusion recovery and hemostatic function. In this study, we established a model of mitochondrial injury that resembles platelet storage lesion. Mitochondrial injury, provoked by incubation of platelets with carbonyl cyanide m-chlorophenylhydrazone (CCCP), led to reduced posttransfusion recovery in mice, an effect that directly correlated with the duration of treatment. Damaged platelets were characterized by shape change, disruption of membrane asymmetry, surface expression of Pselectin, and profound proteolysis of GPIb␣. Using our model, we identified a key role for endogenous metalloproteinase(s) in platelet clearance, as their inhibition markedly improved posttransfusion recovery of both the mitochondriainjured and in vitro-aged mouse platelets. Metalloproteinase inhibition also prevented proteolysis of GPIb␣ on damaged platelets, thereby improving the hemostatic function of these cells in vivo. We propose that inhibition of metalloproteinase activity during storage could significantly improve the effectiveness of platelet transfusions. Surface expression of GPIb␣ might be a powerful marker to determine the quality of platelet concentrates, because it reflects metalloproteinase activity in vitro. IntroductionPlatelet concentrates (PCs) are widely used to support patients who receive intensive therapies for hematologic malignancies and solid tumors. 1 Platelets in PCs undergo a number of events during collection, processing, and storage that adversely affect their structure and function, resulting in reduced posttransfusion recovery. 2 The observed changes are summarized as platelet storage lesion (PSL) and are indicative of partial platelet activation, including the rearrangement of the platelet cytoskeleton, microvesiculation, translocation of phosphatidyl serine (PS) to the outer leaflet of the plasma membrane, and surface expression of Pselectin. 3 GPIb-V-IX, a surface receptor mediating primary adhesion of circulating platelets to a thrombogenic surface, 4 is also affected during PSL. As shown by various groups, long-term storage induces proteolysis of an approximately 130-kDa fragment (glycocalicin) of the GPIb␣ subunit from the receptor complex. [5][6][7] The protease(s) involved in the cleavage and their relevance to platelet survival in vivo, however, remain elusive. The shelf-life of PCs is currently limited to 5 days by the risk of bacterial contamination rather than the quality of the stored platelets. However, as new methods of pathogen inactivation are currently tested for clinical use, 8,9 the potential of prolonged PC storage raises questions about what determines the survival of platelets in vivo and how PC quality can be accurately assessed in vitro.Microvesiculation and PS exposure are also hallmark characteristics of apoptosis, a physiologic program for the safe elimination of cells. In most pathway...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro–aged or –injured mouse platelets

Bergmeier

Burger

Piffath

et al. 2003

Blood

159

178

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“…Platelets contain and release MMP-2, a gelatinase, which acts as a stimulator 31 of aggregation. Therefore, we studied the gelatinolytic activity of MMP-2 released from QD-activated platelets by gelatin gel zymography ( Figure 3A) and quantified the resultant bands ( Figure 3B).…”

Section: Qds Induce Mmp-2 Release From Plateletsmentioning

confidence: 99%

“…48 Most of these studies were performed using LTA. We have shown that LTA may not be sensitive enough for studying platelet-NP interactions, and a more [29][30][31][32][33] may be preferred. In keeping with this notion, we detected QD-induced platelet aggregation in PRP using QCM-D but not LTA.…”

mentioning

confidence: 99%

CdTe quantum dots induce activation of human platelets: implications for nanoparticle hemocompatibility

Samuel¹,

Santos-Martínez²,

Medina³

et al. 2015

IJN

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New nanomaterials intended for systemic administration have raised concerns regarding their biocompatibility and hemocompatibility. Quantum dots (QD) nanoparticles have been used for diagnostics, and recent work suggests their use for in vivo molecular and cellular imaging. However, the hemocompatibility of QDs and their constituent components has not been fully elucidated. In the present study, comprehensive investigation of QD–platelet interactions is presented. These interactions were shown using transmission electron microscopy. The effects of QDs on platelet function were investigated using light aggregometry, quartz crystal microbalance with dissipation, flow cytometry, and gelatin zymography. Platelet morphology was also analyzed by phase-contrast, immunofluorescence, atomic-force and transmission electron microscopy. We show that the QDs bind to platelet plasma membrane with the resultant upregulation of glycoprotein IIb/IIIa and P-selectin receptors, and release of matrix metalloproteinase-2. These findings unravel for the first time the mechanism of functional response of platelets to ultrasmall QDs in vitro.

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MMP‐13 binds to platelet receptors αIIbβ3 and GPVI and impairs aggregation and thrombus formation

Howes

Pugh

Hamaia

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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Essentials MMP‐13 has the potential to influence platelet function and thrombus formation directly.We sought to elucidate whether MMP‐13 is able to bind to specific platelet receptors.MMP‐13 is able to bind to platelet alphaIIbbeta3 (αIIbβ3) and glycoprotein (GP)VI.These interactions are sufficient to inhibit platelet aggregation and thrombus formation. BackgroundAcute thrombotic syndromes lead to atherosclerotic plaque rupture with subsequent thrombus formation, myocardial infarction and stroke. Following rupture, flowing blood is exposed to plaque components, including collagen, which triggers platelet activation and aggregation. However, plaque rupture releases other components into the surrounding vessel which have the potential to influence platelet function and thrombus formation.ObjectivesHere we sought to elucidate whether matrix metalloproteinase‐13 (MMP‐13), a collagenolytic metalloproteinase up‐regulated in atherothrombotic and inflammatory conditions, affects platelet aggregation and thrombus formation.ResultsWe demonstrate that MMP‐13 is able to bind to platelet receptors alphaIIbbeta3 (αIIbβ3) and platelet glycoprotein (GP)VI. The interactions between MMP‐13, GPVI and αIIbβ3 are sufficient to significantly inhibit washed platelet aggregation and decrease thrombus formation on fibrillar collagen.ConclusionsOur data demonstrate a role for MMP‐13 in the inhibition of both platelet aggregation and thrombus formation in whole flowing blood, and may provide new avenues of research into the mechanisms underlying the subtle role of MMP‐13 in atherothrombotic pathologies.

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Localization and Translocation of MMP-2 during Aggregation of Human Platelets

Cited by 104 publications

References 19 publications

Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro–aged or –injured mouse platelets

Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro–aged or –injured mouse platelets

CdTe quantum dots induce activation of human platelets: implications for nanoparticle hemocompatibility

MMP‐13 binds to platelet receptors αIIbβ3 and GPVI and impairs aggregation and thrombus formation

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