P-Selectin Expression on Platelets Determines Size and Stability of Platelet Aggregates

Merten, Michael; Thiagarajan, Perumal

doi:10.1161/01.cir.102.16.1931

Cited by 257 publications

(194 citation statements)

References 33 publications

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“…The aggregation of platelets under flow conditions indicated that interfering with P-selectin decreases the stability and size of aggregates. Our data and those published by others 10,48 show that P-selectin plays an important role in thrombus stability and aggregate size in vitro and in vivo. Therefore, the use of small-molecular compounds that decrease stability and size of thrombi, but do not impair hemostasis, is of therapeutic interest.…”

Section: Discussionsupporting

confidence: 87%

“…Previous studies have suggested that P-selectin expression on platelets (it is the only selectin expressed by platelets) may influence the size and stability of thrombi. [10][11][12] Based upon comparisons between P-selectin-deficient and wild-type mice, it has recently been suggested that P-selectin expressed on activated platelets contributes to myocardial reperfusion injury. 13 However, the exact role of P-selectin in these processes is not clear, and its use as a therapeutic target structure has not been established.…”

mentioning

confidence: 99%

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Diminished thrombus formation and alleviation of myocardial infarction and reperfusion injury through antibody- or small-molecule-mediated inhibition of selectin-dependent platelet functions

Oostingh

Požgajová²,

Ludwig³

et al. 2007

Haematologica

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BACKGROUND AND OBJECTIVES: P-selectin ctin has been implicated in important platelet functions. However, neither its role in thrombus formation and cardiovascular disorders nor its suitability as a therapeutic target structure is entirely clear. DESIGN AND METHODS: Platelet aggregation was assessed in complementary in vitro settings by measurements of static aggregation, standardized aggregometry and dynamic flow chamber assays. Degradation of aggregates was also analyzed under flow conditions using video microscopy. In vivo, platelet rolling in cutaneous venules was assessed by intravital microscopy in wild-type mice treated with selectin-blocking compounds as well as in P-selectin-deficient mice. FeCl3-induced arterial thrombosis was studied by intravital microscopy in untreated mice or mice treated with an inhibitor of selectin functions. Finally, inhibition of selectin functions was studied in an ischemia/reperfusion injury model in rats. RESULTS: Antibody- or small-molecule-mediated inhibition of P-selectin functions significantly diminished platelet aggregation (p<0.03) and platelet-neutrophil adhesion in vitro (p<0.01) as well as platelet aggregate sizes under flow (p<0.03). Established aggregates were degraded, either via detachment of single platelets following addition of efomycine M, or via detachment of multicellular clumps when P-selectin-directed Fab-fragments were used. In vivo, selectin inhibition resulted in a greater than 50% reduction of platelet rolling in cutaneous venules (p<0.01), producing rolling fractions similar to those observed in P-selectin-deficient mice (p<0.05). Moreover, inhibition of selectin functions significantly decreased the thrombus size in FeCl3-induced arterial thrombosis in mice (p<0.05). In an ischemia/reperfusion injury model in rats, small-molecule-mediated selectin inhibition significantly reduced myocardial infarct size from 18.9% to 9.42% (p<0.001) and reperfusion injury (p<0.001). INTERPRETATION AND CONCLUSIONS: Inhibition of P-selectin functions reduces platelet aggregation and can alleviate platelet-related disorders in disease-relevant preclinical settings

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Section: Discussionsupporting

confidence: 87%

mentioning

confidence: 99%

Diminished thrombus formation and alleviation of myocardial infarction and reperfusion injury through antibody- or small-molecule-mediated inhibition of selectin-dependent platelet functions

Oostingh

Požgajová²,

Ludwig³

et al. 2007

Haematologica

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“…Supporting this hypothesis, increased P-selectin levels have been reported to be associated with cardiovascular disorders in several studies (Barbaux et al 2001;Blann et al 1997;Ikeda et al 1995;Merten & Thiagarajan, 2000;Ridker et al 2000). By acting as a counterligand for P-selectin, SELPLG is suspected to be involved in the atherosclerosis process.…”

Section: Introductionmentioning

confidence: 87%

SELPLG Gene Polymorphisms in Relation to Plasma SELPLG Levels and Coronary Artery Disease

Trégouët

Barbaux

Poirier

et al. 2003

Annals of Human Genetics

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SummaryP-selectin and P-selectin glycoprotein ligand (SELPLG, selectin P ligand) constitute a receptor/ligand complex that is likely to be involved in the development of atherosclerosis and its complications. While the genetic variability of P-selectin has already been investigated in depth, that of the SELPLG gene has not yet been extensively explored. The coding and regulatory sequences of the SELPLG were screened and nine polymorphisms were identified. The identified polymorphisms were genotyped in the AtheroGene study, a case-control study of coronary artery disease (CAD). Haplotype analysis revealed that two polymorphisms of SELPLG, the M62I and the VNTR, independently influenced plasma SELPLG levels. Conversely, haplotypes of SELPLG were not associated with CAD risk.

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“…It is involved in mediating platelets and the rolling of leukocytes on activated endothelial cells [45,46] as well as in interactions of activated platelets with leukocytes. Other studies also demonstrated that the size of the aggregated platelets and the immobilization of platelets on the clots depend on P-selectin [47].…”

Section: Selectinmentioning

confidence: 89%

The Recent Advances in the Serological Detection of Acute Myocardial Infarction

Gh¹,

Ac²

2016

Clin Med Biochemistry

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Acute Myocardial Infarction (AMI) is one of the leading causes of morbidity and mortality worldwide. The greatest risk of fatality occurs within the first hours of initiation of AMI. Thus, the early diagnosis of cardiac ischemia is fundamental for the effective management of AMI patients. Inadequate diagnosis of patients with chest pain often leads to inadequate admission of patients without AMI and vice versa. In addition to the clinical history, physical examination, accurate electrocardiogram findings, and evaluation of cardiac biomarkers play an important role in the early diagnosis of acute ischemia. The present review discusses in detail the various cardiac biomarkers released during the event of an AMI.

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P-Selectin Expression on Platelets Determines Size and Stability of Platelet Aggregates

Abstract: These results indicate that P-selectin interaction with a ligand, different from PSGL-1 or GP Ib, stabilizes initial GP IIb/IIIa-fibrinogen interactions, allowing the formation of large stable platelet aggregates.

Cited by 257 publications

References 33 publications

Diminished thrombus formation and alleviation of myocardial infarction and reperfusion injury through antibody- or small-molecule-mediated inhibition of selectin-dependent platelet functions

Diminished thrombus formation and alleviation of myocardial infarction and reperfusion injury through antibody- or small-molecule-mediated inhibition of selectin-dependent platelet functions

SELPLG Gene Polymorphisms in Relation to Plasma SELPLG Levels and Coronary Artery Disease

The Recent Advances in the Serological Detection of Acute Myocardial Infarction

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