Elastin-Derived Peptides Are New Regulators of Thrombosis

Kawecki, Charlotte; Hézard, Nathalie; Bocquet, Olivier; Poitevin, Gael; Rabenoelina, Fanja; Kauskot, Alexandre; Duca, Laurent; Blaise, Sébastien; Romier, Béatrice; Martiny, Laurent; Nguyên, Philippe; Debelle, Laurent; Maurice, Pascal

doi:10.1161/atvbaha.114.304432

Cited by 37 publications

(25 citation statements)

References 32 publications

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“…For example, a typical feature of vascular ageing and the progression of a range of vascular diseases are the degradation of extracellular matrix and the release of elastin-derived peptides (EDP) into the circulation (Antonicelli et al 2007 ; Fulop et al 2012 ; Maurice et al 2013 ). Recent work has shown that kappa-elastin (a complex mixture of approximately 29 EDPs) inhibited platelet aggregation to multiple agonists and prolonged occlusion time in a FeCl 3 -induced model of thrombosis in mouse mesenteric arterioles (Kawecki et al 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Platelet function and ageing

Jones

2016

Mamm Genome

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There are clear age-related changes in platelet count and function, driven by changes in hematopoietic tissue, the composition of the blood and vascular health. Platelet count remains relatively stable during middle age (25–60 years old) but falls in older people. The effect of age on platelet function is slightly less clear. The longstanding view is that platelet reactivity increases with age in an almost linear fashion. There are, however, serious limitations to the data supporting this dogma. We can conclude that platelet function increases during middle age, but little evidence exists on the changes in platelet responsiveness in old age (>75 years old). This change in platelet function is driven by differential mRNA and microRNA expression, an increase in oxidative stress and changes in platelet receptors. These age-related changes in platelets are particularly pertinent given that thrombotic disease and use of anti-platelet drugs is much more prevalent in the elderly population, yet the majority of platelet research is carried out in young to middle-aged (20–50 years old) human volunteers and young mice (2–6 months old). We know relatively little about exactly how platelets from people over 75 years old differ from those of middle-aged subjects, and we know even less about the mechanisms that drive these changes. Addressing these gaps in our knowledge will provide substantial understanding in how cell signalling changes during ageing and will enable the development of more precise anti-platelet therapies.

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Section: Introductionmentioning

confidence: 99%

Platelet function and ageing

Jones

2016

Mamm Genome

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“…Meanwhile, a group of standard mixtures were prepared. The absorbance of these solutions was estimated at 490 nm and the blood volumes were calculated with standard curve [ 15 , 16 ].…”

Section: Methodsmentioning

confidence: 99%

Antiplatelet Aggregation and Antithrombosis Efficiency of Peptides in the Snake Venom ofDeinagkistrodon acutus: Isolation, Identification, and Evaluation

Ding

Jiang

et al. 2015

Evidence-Based Complementary and Alternative Medicine

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Two peptides of Pt-A (Glu-Asn-Trp 429 Da) and Pt-B (Glu-Gln-Trp 443 Da) were isolated from venom liquor of Deinagkistrodon acutus. Their antiplatelet aggregation effects were evaluated with platelet-rich human plasma in vitro; the respective IC50 of Pt-A and Pt-B was 66 μM and 203 μM. Both peptides exhibited protection effects on ADP-induced paralysis in mice. After ADP administration, the paralysis time of different concentration of Pt-A and Pt-B lasted as the following: 80 mg/kg Pt-B (152.8 ± 57.8 s) < 40 mg/kg Pt-A (163.5 ± 59.8 s) < 20 mg/kg Pt-A (253.5 ± 74.5 s) < 4 mg/kg clopidogrel (a positive control, 254.5 ± 41.97 s) < 40 mg/kg Pt-B (400.8 ± 35.9 s) < 10 mg/kg Pt-A (422.8 ± 55.4 s), all of which were statistically shorter than the saline treatment (666 ± 28 s). Pulmonary tissue biopsy confirmed that Pt-A and Pt-B prevented the formation of thrombi in the lung. Unlike ADP injection alone, which caused significant reduction of peripheral platelet count, Pt-A treatment prevented the drop of peripheral platelet counts; interestingly, Pt-B could not, even though the same amount of Pt-B also showed protection effects on ADP-induced paralysis and thrombosis. More importantly, intravenous injection of Pt-A and Pt-B did not significantly increase the hemorrhage risks as clopidogrel.

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“…In a recent study published by Kawecki et al (2014) , EDP were shown to decrease human platelet aggregation in whole blood and washed platelets. Both EDP and the VGVAPG peptide strongly reduced thrombus formation in vitro and in vivo in wild-type mice.…”

Section: Erc Involvement In Cancer-associated Processesmentioning

confidence: 95%

The Elastin Receptor Complex: A Unique Matricellular Receptor with High Anti-tumoral Potential

et al. 2016

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Elastin, one of the longest-lived proteins, confers elasticity to tissues with high mechanical constraints. During aging or pathophysiological conditions such as cancer progression, this insoluble polymer of tropoelastin undergoes an important degradation leading to the release of bioactive elastin-derived peptides (EDPs), named elastokines. EDP exhibit several biological functions able to drive tumor development by regulating cell proliferation, invasion, survival, angiogenesis, and matrix metalloproteinase expression in various tumor and stromal cells. Although, several receptors have been suggested to bind elastokines (αvβ3 and αvβ5 integrins, galectin-3), their main receptor remains the elastin receptor complex (ERC). This heterotrimer comprises a peripheral subunit, named elastin binding protein (EBP), associated to the protective protein/cathepsin A (PPCA). The latter is bound to a membrane-associated protein called Neuraminidase-1 (Neu-1). The pro-tumoral effects of elastokines have been linked to their binding onto EBP. Additionally, Neu-1 sialidase activity is essential for their signal transduction. Consistently, EDP-EBP interaction and Neu-1 activity emerge as original anti-tumoral targets. Interestingly, besides its direct involvement in cancer progression, the ERC also regulates diabetes outcome and thrombosis, an important risk factor for cancer development and a vascular process highly increased in patients suffering from cancer. In this review, we will describe ERC and elastokines involvement in cancer development suggesting that this unique receptor would be a promising therapeutic target. We will also discuss the pharmacological concepts aiming at blocking its pro-tumoral activities. Finally, its emerging role in cancer-associated complications and pathologies such as diabetes and thrombotic events will be also considered.

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Elastin-Derived Peptides Are New Regulators of Thrombosis

Cited by 37 publications

References 32 publications

Platelet function and ageing

Platelet function and ageing

Antiplatelet Aggregation and Antithrombosis Efficiency of Peptides in the Snake Venom ofDeinagkistrodon acutus: Isolation, Identification, and Evaluation

The Elastin Receptor Complex: A Unique Matricellular Receptor with High Anti-tumoral Potential

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