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

Bergmeier, Wolfgang; Burger, Peter C.; Piffath, Crystal L.; Hoffmeister, Karin M.; Hartwig, John H.; Nieswandt, Bernhard; Wagner, Denisa D.

doi:10.1182/blood-2003-04-1305

Cited by 159 publications

(204 citation statements)

References 48 publications

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“…Mouse platelets were isolated as described in ref. 60, labeled with calcein-AM (Molecular Probes), and injected intravenously immediately before observation. Anesthetized mice were placed in left lateral decubital position on a Plexiglas pad; skin-fold chamber was locked into a fixed position, and vessels were visualized using an intravital microscope (Zeiss Axioplan) equipped with an intensified charge-coupled device video camera as described in ref.…”

Section: Methodsmentioning

confidence: 99%

Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage

Kisucka

Butterfield

Duda

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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326

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Platelets contain both pro-and antiangiogenic factors, but their regulatory role in angiogenesis is poorly understood. Although previous studies showed that platelets stimulate angiogenesis in vitro, the role of platelets in angiogenesis in vivo is largely uncharacterized. To address this topic, we used two in vivo approaches, the cornea micropocket assay and the Matrigel model, in four animal models: thrombocytopenic, Lyst bg (platelet storage pool deficiency), glycoprotein (GP) Ib␣͞IL4R transgenic (lacking extracellular GPIb␣, the receptor for von Willebrand factor as well as other adhesive and procoagulant proteins), and Fc␥R ؊/؊ (lacking functional GPVI, the collagen receptor) mice. Adult mice were rendered thrombocytopenic by i.p. administration of an antiplatelet antibody. The number of growing vessels in the thrombocytopenic mice was lower in the cornea assay, and they showed significantly increased appearance of hemorrhage compared with mice treated with control IgG. The thrombocytopenic mice also showed more protein leakage and developed hematomas in the Matrigel model. GPIb␣͞IL4R transgenic mice presented increased hemorrhage in both assays, but it was less severe than in the platelet-depleted mice. Fc␥R ؊/؊ and Lyst bg mice showed no defect in experimental angiogenesis. Intravital microscopy revealed a >3-fold increase in platelet adhesion to angiogenic vessels of Matrigel compared with mature quiescent skin vessels. Our results suggest that the presence of platelets not only stimulates angiogenic vessel growth but also plays a critical role in preventing hemorrhage from the angiogenic vessels. The adhesion function of platelets, as mediated by GPIb␣, significantly contributes to the process. thrombocytopenic mice ͉ blood vessel ͉ ␣-granule ͉ cornea ͉ collagen receptor

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Section: Methodsmentioning

confidence: 99%

Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage

Kisucka

Butterfield

Duda

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

326

241

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“…Much of the current effort into improving the viability of stored platelet concentrates has focused on reducing platelet activation, maintaining pH, buffering lactate production and enhancing gas exchange. This has been achieved with the use of platelet activation inhibitors (NO, phosphodiesterase inhibitors, apyrase and prostacyclin, protease inhibitors), [50][51][52][53][54][55][56][57] through inclusion of additives such as acetate, phosphate, gluconate, potassium, and magnesium 41,[43][44][45][46][47][58][59][60] and through the implementation of modified storage bags with agitation. 61 However, these measures have provided only modest improvements in platelet viability.…”

Section: Apoptotic and Necrotic Death Pathways: Implications For The mentioning

confidence: 99%

Procoagulant platelets: are they necrotic?

Jackson

Schoenwaelder

2010

Blood

142

141

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Apoptosis and necrosis represent distinct cell death processes that regulate mammalian development, physiology and disease. Apoptosis characteristically leads to the silent destruction and removal of cells in the absence of an inflammatory response. In contrast, necrotic cell death can induce physiologic inflammatory responses linked to tissue defense and repair. Although anucleate, platelets undergo programmed cell death, with apoptosis playing an important role in clearing effete platelets from the circulation. While it has long been recognized that procoagulant platelets exhibit characteristic features of dying cells, recent studies have demonstrated that platelet procoagulant function can occur independent of apoptosis. A growing body of evidence suggest that the biochemical, morphologic and functional changes underlying agonist-induced platelet procoagulant function are broadly consistent with cell necrosis, raising the possibility that distinct death pathways regulate platelet function and survival. In this article, we will discuss the mechanisms underlying apoptotic and necrotic cell death pathways and examine the evidence linking these pathways to the platelet procoagulant response. We will also discuss the potential contribution of these pathways to the platelet storage lesion and propose a simplified nomenclature to describe procoagulant platelets. IntroductionUntil the early 1970s it was thought that all cells die as a result of necrosis (Table 1); a form of cell death that is prominent when tissues undergo extensive damage from trauma or disease. This concept changed dramatically in 1972 after the landmark observations of Kerr and colleagues, 9 who described a new form of cell death, termed apoptosis (Table 1). Since then, the genetic and biochemical processes responsible for apoptotic cell death have been extensively investigated. It is now well defined that apoptosis is a key process underlying human development, normal physiology and a range of common human diseases. 10 In contrast, the concepts underlying necrosis have become less clear-cut. While it has long been assumed that necrosis is predominantly a pathologic process resulting from tissue injury, there is growing evidence that cells can orchestrate their own demise through programmed cell necrosis in a manner that initiates physiologic inflammatory and repair responses. [2][3][4][6][7][8] Although anucleate, platelets have the capacity to undergo programmed cell death (Table 1). This has been most clearly demonstrated with platelet apoptosis; a process that is important for clearance of effete platelets from the circulation. 1,11 Many of the features of apoptosis (membrane fragmentation, cytoskeletal disruption, microvesiculation, caspase activation and phosphatidylserine [PS] exposure) are observed during prolonged platelet storage ex vivo and during the conversion of activated platelets to a procoagulant state, raising the possibility that apoptosis may also regulate platelet function. However, recent studies have demonstrated that the m...

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“…This causes platelet dysfunction, increases the risk of bacterial overgrowth and limits the shelf life of banked platelets to 5 days. 29,30 Recent evidence suggests that the platelet cold storage lesion results from GpIb-IX-V clustering. Transfused platelets with clustered GpIb-IX-V are recognized by αMβ2 (Mac-1) on hepatic and splenic macrophages, which results in their removal from the circula-tion by phagocytosis.…”

Section: Platelet Storagementioning

confidence: 99%

Acquired Disorders of Platelet Function

Hassan

Kroll

2005

Hematology

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A qualitative abnormality of platelet function should be considered in patients with mucocutaneous bleeding in the absence of thrombocytopenia or von Willebrand disease. Antiplatelet drugs are the most common cause of acquired platelet disorders leading to bleeding. Uremia, hepatic cirrhosis, myeloma and related disorders, polycythemia vera, essential thrombocythemia, and cardiopulmonary bypass have long been recognized as clinical situations in which platelet dysfunction may contribute to bleeding. When an acquired platelet disorder is suspected, it is useful to examine platelet function by measuring the bleeding time, examining platelet-dependent closure time in a platelet function analyzer and performing platelet aggregometry. When a specific acquired platelet disorder is diagnosed, many treatment options are available including controlling the underlying disease, giving platelet transfusions and administering a hemostatic drug.

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

Cited by 159 publications

References 48 publications

Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage

Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage

Procoagulant platelets: are they necrotic?

Acquired Disorders of Platelet Function

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