scholarly journals Role of P2Y Receptors in Platelet Extracellular Vesicle Release

2020 ◽  
Vol 21 (17) ◽  
pp. 6065
Author(s):  
Aleksandra Gąsecka ◽  
Sylwester Rogula ◽  
Ceren Eyileten ◽  
Marek Postuła ◽  
Miłosz J. Jaguszewski ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Coronary Thrombosis ◽  
Myocardial Necrosis ◽  
Coronary Intervention ◽  
P2y Receptors ◽  
Extracellular Vesicle ◽  
Research Field ◽  
P2y12 Antagonists ◽  
New Biomarkers

Platelet extracellular vesicles (PEVs) are potential new biomarkers of platelet activation which may allow us to predict and/or diagnose developing coronary thrombosis before myocardial necrosis occurs. The P2Y1 and P2Y12 receptors play a key role in platelet activation and aggregation. Whereas the P2Y1 antagonists are at the preclinical stage, at present, the P2Y12 antagonists are the most effective treatment strategy to prevent stent thrombosis after percutaneous coronary intervention. Despite an increasing number of publications on PEVs, the mechanisms underlying their formation, including the role of purinergic receptors in this process, remain an active research field. Here, we outline the clinical relevance of PEVs in cardiovascular disease, summarize the role and downstream signalling of P2Y receptors in platelet activation, and discuss the available evidence regarding their role in PEV formation.

scholarly journals β-arrestin-1 participates in thrombosis and regulates integrin αIIbβ3 signalling without affecting P2Y receptors desensitisation and function

2012 ◽  
Vol 107 (04) ◽  
pp. 735-748 ◽  
Author(s):  
Mathieu Schaff ◽  
Nicolas Receveur ◽  
Catherine Bourdon ◽  
Philippe Ohlmann ◽  
François Lanza ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Thrombus Formation ◽  
P2y Receptors ◽  
Integrin Αiibβ3 ◽  
Akt Phosphorylation ◽  
Fibrinogen Binding ◽  
And Function ◽  
G Protein Coupled ◽  
Receptor Desensitisation

Summaryβ-arrestin-1 (β-arr1) and β-arrestin-2 (β-arr2) are cytosolic proteins well-known to participate in G protein-coupled receptor desensitisation and signalling. We used genetically-inactivated mice to evaluate the role of β-arr1 or β-arr2 in platelet function, P2Y receptor desensitisation, haemostasis and thrombosis. Platelet aggregation, soluble fibrinogen binding and P-selectin exposure induced by various agonists were near normal in β-arr1−/− and β-arr2−/− platelets. In addition, deficiency in β-arr1 or β-arr2 was not critical for P2Y receptors desensitisation. A functional redundancy between β-arr1 and β-arr2 may explain these unchanged platelet responses. Interestingly, β-arr1−/− but not β-arr2−/− mice were protected against laser- and FeCl3-induced thrombosis. The tail bleeding times, number of rebleeds and volume of blood loss were unchanged in β-arr1−/− and β-arr2−/− mice, suggesting no defect in haemostasis. β-arr1−/− platelet activation upon adhesion to immobilised fibrinogen was inhibited, as attested by a 37 ± 5% (n = 3, p<0.0001) decrease in filopodia extension, suggesting defective signalling through integrin αIIbβ3. β-arr1 appeared to be located downstream of Src family kinases and to regulate αIIbβ3 signalling by increasing Akt phosphorylation. Overall, this study supports a role for β-arr1 in promoting thrombus formation, in part through its participation in αIIbβ3 signalling, and no role of β-arr1 and β-arr2 in agonist-induced platelet activation and P2Y receptors desensitisation.

scholarly journals Thrombosis in COVID-19 infection: Role of platelet activation-mediated immunity

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mahin Behzadi Fard ◽  
Samaneh Behzadi Fard ◽  
Shahin Ramazi ◽  
Amir Atashi ◽  
Zahra Eslamifar
Keyword(s):  
Platelet Activation ◽  
Coronary Thrombosis ◽  
Oxygen Demand ◽  
Main Body ◽  
Lectin Receptor ◽  
Multiple Receptors ◽  
Viral Therapy ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Abstract Background Thrombosis plays an important role in the Coronavrus Disease 2019 (COVID-19) infection-related complications such as acute respiratory distress syndrome and myocardial infarction. Multiple factors such as oxygen demand injuries, endothelial cells injury related to infection, and plaque formation. Main body Platelets obtained from the patients may have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, showing that the increased activation potential recommends platelet can be hyper-activated in severely ill SARS-CoV-2 cases. Platelets contain multiple receptors that interact with specific ligands. Pathogen’s receptors such as Toll-like receptors (TLRs), NOD-like receptor, C-type lectin receptor family, glycoprotein (GP) such as GPαIIbβ3 and GPIbα which allow pathogens to interact with platelets. Platelet TLRs and NOD2 are involved in platelet activation and thrombosis. Accordingly, TLRs are critical receptors that could recognize various endogenous damage-associated molecular patterns and exogenous pathogen-associated molecular patterns (PAMPs). TLRs are considered as important components in the activation of innate immunity response against pathogenic and non-pathogenic components like damaged tissues. TLRs-1,-2,-4,-6,-7 expression on or within platelets has been reported previously. Various PAMPs were indicated to be capable of binding to platelet-TLRs and inducing both the activation and promotion of downstream proinflammatory signaling cascade. Conclusion It is possible that the increased TLRs expression and TLR-mediated platelets activation during COVID-19 may enhance vascular and coronary thrombosis. It may be hypothesized using TLRs antagonist and monoclonal antibody against P-selectin, as the marker of leukocyte recruitment and platelet activation, besides viral therapy provide therapeutic advances in fighting against the thrombosis related complications in COVID-19.

scholarly journals miRNAs as Key Players in the Management of Cutaneous Melanoma

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 415 ◽  
Author(s):  
Celeste Lorusso ◽  
Simona De Summa ◽  
Rosamaria Pinto ◽  
Katia Danza ◽  
Stefania Tommasi
Keyword(s):  
Biological Networks ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Mirna Gene ◽  
Progression Free Survival ◽  
Extracellular Vesicle ◽  
Resistance Mechanisms ◽  
Melanoma Patients ◽  
New Biomarkers

The number of treatment options for melanoma patients has grown in the past few years, leading to considerable improvements in both overall and progression-free survival. Targeted therapies and immune checkpoint inhibitors have opened a new era in the management of melanoma patients. Despite the clinical advances, further research efforts are needed to identify other “druggable” targets and new biomarkers to improve the stratification of melanoma patients who could really benefit from targeted and immunotherapies. To this end, many studies have focused on the role of microRNAs (miRNAs) that are small non-coding RNAs (18-25 nucleotides in length), which post-transcriptionally regulate the expression of their targets. In cancer, they can behave either as oncogenes or oncosuppressive genes and play a central role in many intracellular pathways involved in proliferation and invasion. Given their modulating activity on the transcriptional landscape, their biological role is under investigation to study resistance mechanisms. They are able to mediate the communication between tumor cells and their microenvironment and regulate tumor immunity through direct regulation of the genes involved in immune activation or suppression. To date, a very promising miRNA-based strategy is to use them as prognosis and diagnosis biomarkers both as cell-free miRNAs and extracellular-vesicle miRNAs. However, miRNAs have a complex role since they target different genes in different cellular conditions. Thus, the ultimate aim of studies has been to recapitulate their role in melanoma in biological networks that account for miRNA/gene expression and mutational state. In this review, we will provide an overview of current scientific knowledge regarding the oncogenic or oncosuppressive role of miRNAs in melanoma and their use as biomarkers, with respect to approved therapies for melanoma treatment.

On The Mechanism Of Heparin-Induced Potentiation Of Platelet Aggregation

1981 ◽  
Author(s):  
M Yamamoto ◽  
K Watanabe ◽  
Y Ando ◽  
H Iri ◽  
N Fujiyama ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Coagulation Factors ◽  
Marked Enhancement ◽  
Matrix Bound ◽  
Induced Aggregation ◽  
Aggregation Of Platelets ◽  
Plasma Heparin

It has been suggested that heparin caused potentiation of aggregation induced by ADP or epinephrine. The exact mechanism of heparin-induced platelet activation, however, remained unknown. In this paper, we have investigated the role of anti-thrombin III ( AT ) in heparin-induced platelet activation using purified AT and AT depleted plasma. When ADP or epinephrine was added to citrated PRP one minute after addition of heparin ( 1 u/ml, porcine intestinal mucosal heparin, Sigma Co. USA ), marked enhancement of platelet aggregation was observed, compared with the degree of aggregation in the absence of heparin. However, in platelet suspensions prepared in modified Tyrode’s solution, heparin exhibited no potentiating effect on platelet aggregation induced by epinephrine or ADP. Potentiation of epinephrine- or ADP-induced platelet aggregation by heparin was demonstrated when purified AT was added to platelet suspensions at a concentration of 20 μg/ml. AT depleted plasma, which was prepared by immunosorption using matrix-bound antibodies to AT, retained no AT, while determination of α1-antitrypsinα2- macroglobulin and fibrinogen in AT depleted plasma produced values which corresponded to those of the original plasma when dilution factor was taken into account. The activities of coagulation factors were also comparable to those of the original plasma. Heparin exhibited potentiating effect on ADP- or epinephrine-induced aggregation of platelets in original plasma, but no effect in AT depleted plasma. When purified AT was added back to AT depleted plasma at a concentration of 20 μg/ml, potentiation of platelet aggregation by heparin was clearly demonstrated.Our results suggest that effect of heparin on platelet aggregation is also mediated by anti-thrombin III.

Coronary Intervention with the Excimer Laser: Review of the Technology and Outcome Data

2016 ◽  
Vol 11 (1) ◽  
pp. 27
Author(s):  
John Rawlins ◽  
◽  
◽  
◽  
◽  
...  
Keyword(s):  
Excimer Laser ◽  
Coronary Intervention ◽  
Outcome Data ◽  
Boston Scientific ◽  
Technical Aspects ◽  
Safety And Efficacy ◽  
Percutaneous Coronary ◽  
Short Period ◽  
Complex Lesions

Excimer laser coronary atherectomy (ELCA) is a long-established adjunctive therapy that can be applied during percutaneous coronary intervention (PCI). Technical aspects have evolved and there is an established safety and efficacy record across a number of clinical indications in contemporary interventional practice where complex lesions are routinely encountered. The role of ELCA during PCI for thrombus, non-crossable or non-expandable lesions, chronic occlusions and stent under-expansion are discussed in this review. The key advantage of ELCA over alternative atherectomy interventions is delivery on a standard 0.014-inch guidewire. Additionally, the technique can be mastered by any operator after a short period of training. The major limitation is presence of heavy calcification although when rotational atherectomy (RA) is required but cannot be applied due to inability to deliver the dedicated RotaWire™ (Boston Scientific), ELCA can create an upstream channel to permit RotaWire passage and complete the case with RA – the RASER technique.

Genetic predictors for symptoms recurrenсe in coronary artery disease after percutaneous coronary intervention

2017 ◽  
pp. 81-86
Author(s):  
Г.А. Березовская ◽  
Е.С. Клокова ◽  
Н.Н. Петрищев
Keyword(s):  
Coronary Artery Disease ◽  
Percutaneous Coronary Intervention ◽  
Coronary Artery ◽  
Coronary Intervention ◽  
Folate Metabolism ◽  
Genotype Distribution ◽  
Polymorphic Markers ◽  
Percutaneous Coronary ◽  
Artery Disease

Гены тромбообразования и фолатного обмена играют важную роль в развитии и прогрессии ишемической болезни сердца (ИБС). Однако о возможной роли полиморфных маркеров в рецидиве ИБС после чрескожного коронарного вмешательства (ЧКВ) известно недостаточно. Цель исследования: Оценить роль генетических факторов системы тромбообразования и фолатного обмена (полиморфных маркеров генов F5, F2, F13A1, PAI1, HPA1, MTHFR, FGB ), в возобновление клиники ИБС после ЧКВ. Методика: Исследование проводили с использованием выборки из 90 больных ИБС в возрасте от 40 до 75 лет: 75 пациентов после планового ЧКВ (60 мужчин и 15 женщин) и 15 лиц после экстренного ЧКВ (12 мужчин и 3 женщины). Молекулярно-генетическое исследование было выполнено с помощью комплекта реагентов «Сердечно-сосудистые заболевания СтрипМетод»® (ViennaLab Diagnostics GmbH, Австрия), выявляющие следующие варианты: F5, F2, F13A1, PAI1, HPA1, MTHFR, FGB . Результаты: В результате исследования была показана ассоциация полиморфного маркера G103T ( Val34Leu ) гена F13A1 (фактор свертываемости крови 13, субъединица A1) с развитием рецидивирующего состояния ИБС после ЧКВ. Выявлены статистически значимые различия в распределении частот генотипов полиморфного маркера Val34Leu гена F13A1 . Показано, что частота генотипа Val/Val у пациентов с осложнениями была выше, чем у пациентов без таковых: 0,700 и 0,400 соответственно (c = 7,78; p = 0,020), при этом генотип Val/Val проявил себя как фактор риска развития осложнений: ОШ = 3,50 (95%ДИ 1,37-8,93). При сравнении аллелей выявили, что частота аллеля L у больных с осложнениями была ниже, чем у лиц без таковых: 0,167 и 0,375 соответственно (p = 0,004), и носительство аллеля L уменьшало вероятность развития осложнений: ОШ = 0,33 (95%ДИ 0,15-0,72). Заключение: Носительство варианта 34V гена F13A1 , кодирующего A-субъединицу фактора свёртывания 13, предрасполагает к возобновлению клинических проявлений ИБС после ЧКВ. Genes of thrombosis and folate metabolism play an important role in development and progression of coronary artery disease (CAD). However, a possible role of polymorphic markers in CAD relapse following percutaneous coronary intervention (PCI) is not sufficiently understood. Background. Reports have indicated an association of genetic factors generally related with thrombophilia and recurrence of symptoms for coronary artery disease (CAD) following a percutaneous coronary intervention (PCI) due to restenosis and in-stent thrombosis. However, the relapse can also be caused by progression of atherosclerosis and endothelial dysfunction in unoperated blood vessels. Aim: To assess the role of genetic risk factors involved in thrombosis and folate metabolism (polymorphic markers of F5, F2, F13A1, PAI1, HPA1, MTHFR, and FGB genes) in recurrence of CAD symptoms after PCI. Methods: The study included 90 patients with CAD aged 40-75; 75 of these patients had undergone elective PCI (60 men and 15 women) and 15 patients - emergency PCI (12 men and 3 women). Molecular genetic tests were performed using a CVD StripAssays® reagent kit (ViennaLab Diagnostics GmbH, Austria) to identify the following genetic variations: F5, F2, F13A1, PAI1, HPA1, MTHFR, and FGB . Results: The study results showed a significant association of the G103T ( Val34Leu ) polymorphism in the F13A1 gene with relapses of IHD after PCI. Significant differences were found in genotype distribution frequencies of the Val34Leu polymorphism in the F13A1 gene. The frequency of Val / Val genotype was higher in patients with complications than without complications, 0.700 and 0.400, respectively (c = 7.78, p = 0.020). Furthermore, the Val/Val genotype can be classified as a risk factor for complications (OR = 3.50; 95% CI, 1.37-8.93). The L allele frequency was lower in patients with complications than in those without complications (0.167 and 0.375, respectively, p = 0.004), and carriage of the L allele reduced the likelihood of complications (OR = 0.33; 95% CI 0.15-0.72). Conclusion: Carriage of the 34V variant in the F13A1 gene that encodes the coagulation factor XIII A subunit predisposes to a relapse of CAD symptoms after PCI.

Role of Calcium in Platelet Activation: Novel Insights and Pharmacological Implications

2016 ◽  
Vol 12 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Periklis Davlouros ◽  
Ioanna Xanthopoulou ◽  
Nikolaos Mparampoutis ◽  
Georgios Giannopoulos ◽  
Spyridon Deftereos ◽  
...  
Keyword(s):  
Platelet Activation

Lipopolysaccharide induces platelet activation in HIV patients: the role of different viral load patterns

HIV Medicine ◽  
2021 ◽  
Author(s):  
Cristina Nocella ◽  
Ivano Mezzaroma ◽  
Vittoria Cammisotto ◽  
Valentina Castellani ◽  
Cinzia Milito ◽  
...  
Keyword(s):  
Viral Load ◽  
Platelet Activation ◽  
Hiv Patients

scholarly journals A Study on the Integration of Resilience and Smart City Concepts in Urban Systems

2021 ◽  
Vol 6 (2) ◽  
pp. 24
Author(s):  
Anastasia Tzioutziou ◽  
Yiannis Xenidis
Keyword(s):  
Smart City ◽  
Research Field ◽  
Urban Systems ◽  
City Management ◽  
Urban Resilience ◽  
Continuous Growth ◽  
Management And Development ◽  
The Many ◽  
Development And Management

The continuous growth of cities brings out various concerns for improved development and management of the multifaceted urban systems, including those of resilience and smartness. Despite the many significant efforts in the research field, both notions remain changeable, thus retaining the lack of commonly accepted conceptual and terminological frameworks. The paper’s research goals are to designate the current direct and indirect links in the conceptualizations and research trends of the resilience and smart city frameworks and to prove the potential of the conceptual convergence between them in the context of urban systems. The application of a semi-systematic literature review, including bibliometric evidence and followed by content analysis, has led to the observation that as the resilience discourse opens up to embrace other dimensions, including technology, the smart city research turns its interest to the perspective of urban protection. Therefore, both concepts share the goal for urban sustainability realized through specific capacities and processes and operationalized with the deployment of technology. The paper’s findings suggest that the conceptual and operational foundations of these two concepts could support the emergence of an integrated framework. Such a prospect acknowledges the instrumental role of the smart city approach in the pursuit of urban resilience and unfolds a new model for sustainable city management and development.

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