Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 15.639
Filtrar
1.
Wiad Lek ; 74(3 cz 1): 471-474, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33813452

RESUMO

OBJECTIVE: The aim: To determine informative value of pre-thrombosis, post-thrombosis and anticoagulation factors as well as their correlations for assessment of hemostasis status in patients with stage VD CKD. PATIENTS AND METHODS: Materials and methods: Potential predictors of thrombophilia development as well as their relationships depending on the level of molecular markers of hemostasis were studied in 88 patients with stage VD CKD undergoing long-term hemodialysis with the view to determine their informative value. RESULTS: Results: Accumulation of soluble fibrin (sF) was demonstrated to cause moderate reaction of D-dimer (D-d) being insufficient in the absence of reaction of anticoagulant component of hemostasis. Soluble fibrin levels were found to be associated with D-d concentration (r = 0.39) and functionally inactive prothrombin forms (FIPF) to some extent (r = -0.24). Accumulation of FIPF in individuals with high level of sF implies significant activation of blood coagulation system at the stage prior to thrombin formation. Absence of close relationship between pre- and post-thrombosis indices may be indicative of still preserved potential of anticoagulant component of hemostasis. CONCLUSION: Conclusions: Accumulation of FIPF is an early marker of activation of blood coagulation and possible thrombosis. Levels of sF correlate with pre-thrombosis (fibrinogen, FIPF) and post-thrombosis (D-d) factors being associated with inhibition of anticoagulation processes. Comprehensive study of basic components of hemostasis in patients with VD stage of chronic kidney disease offer broader opportunities in arranging prophylactic measures to prevent thrombophilia.


Assuntos
Insuficiência Renal Crônica , Trombofilia , Trombose , Biomarcadores , Produtos de Degradação da Fibrina e do Fibrinogênio , Hemostasia , Humanos , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Trombofilia/etiologia , Trombose/etiologia
3.
Medicine (Baltimore) ; 100(13): e25312, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787623

RESUMO

BACKGROUND: Plaque psoriasis (PSO) is a common clinical chronic inflammatory skin disease. The incidence rate is increasing year by year due to the fast pace of work and unhealthy diet. Fire needle has been widely used in the treatment of PSO. However, the efficacy of fire needle for PSO is uncertain. Thus, the purpose of this systematic review is to evaluate the effectiveness and safety of fire needle for PSO (blood stasis syndrome). METHODS: The following electronic databases will be searched from inception to October 2020:PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, WangFang Database, Chinese Science Journal Database, Chinese Biomedical Literature Database. In addition, other documents that meet the requirements will be manually searched, including conference papers, dissertations, etc. All randomized controlled trials using fire needle to treat PSO (blood stasis syndrome) that meet the criteria for inclusion will be included. The primary outcomes are clinical efficacy, Psoriasis area and severity index. Secondary outcomes include Itchy, TCM evaluation standard syndrome score, Dermatological quality of life index, and adverse events. To complete data synthesis and assess the risk of bias, we will use the RevMan V.5.3 software. RESULTS: The review results will be published in a peer-reviewed journal. CONCLUSION: This study will provide high-quality evidence based medicine to evaluate the effectiveness and safety of fire needle for PSO (blood stasis syndrome), and further seek its scientific and effective chinese medicine treatment methods. INPLASY REGISTRATION NUMBER: INPLASY202120007.


Assuntos
Terapia por Acupuntura/métodos , Doenças Hematológicas/terapia , Medicina Tradicional Chinesa/métodos , Psoríase/terapia , Terapia por Acupuntura/instrumentação , Doenças Hematológicas/sangue , Hemostasia , Humanos , Medicina Tradicional Chinesa/instrumentação , Metanálise como Assunto , Agulhas , Psoríase/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Síndrome , Revisões Sistemáticas como Assunto , Resultado do Tratamento
4.
Infez Med ; 29(1): 1-9, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33664168

RESUMO

In this review, we summarize the possible mechanisms of COVID-19-associated coagulopathy and compare its features to other similar conditions. The recent COVID-19 pandemic has caused enormous mortality and morbidity worldwide. It is important to note that COVID-19-associated thrombotic events play a huge role in the morbidity of this disease. Interestingly, it has been observed that this complication may occur despite prophylactic anticoagulant therapy. Recent studies on COVID-19-associated coagulopathy revealed that the COVID-19-associated hypercoagulability is more frequently observed among those with a severe course of the disease. Various mechanisms have been suggested as explanations for this condition and possible underlying etiologies.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , /complicações , /metabolismo , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea/metabolismo , Endotélio Vascular/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hemostasia , Heparina/efeitos adversos , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Receptores de Interleucina-2/sangue , Trombofilia/etiologia , Trombose/etiologia , Fator de Necrose Tumoral alfa/sangue , Internalização do Vírus
5.
Int J Mol Sci ; 22(5)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673634

RESUMO

The beneficial effects of long-chain polyunsaturated omega-3 fatty acids (omega-3 PUFAs) in cardioprotection are widely known and generally accepted. In this literature review, we have focused on the known and postulated mechanisms of action of omega-3 PUFAs and their metabolites on various components of the haemostatic system, in particular on blood platelets and endothelium. We have also made an attempt to provide a comprehensive review of epidemiological studies with particular regard to clinical trials. Notably, the results of these studies are contradictory, and some of them failed to report the beneficial effects of taking or supplementing omega-3 PUFAs in the diet. A potential explanation, in our opinion, could be the need to use higher doses of omega-3 PUFAs and a proper ratio of omega-3 and omega-6 PUFAs. An additional problem which is difficult to solve is the use of a proper neutral placebo for interventional studies. Despite some controversies regarding the beneficial effects of supplementation of omega-3 PUFAs in cardiovascular disease, our review suggests that a promising aspect of future studies and applications is to focus on the anti-thrombotic properties of these compounds. An argument supporting this assumption is the recent use of omega-3 PUFAs as a supporting tool for the treatment of COVID-19 complications.


Assuntos
/complicações , Doenças Cardiovasculares/tratamento farmacológico , Ácidos Graxos Ômega-3/administração & dosagem , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , /tratamento farmacológico , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/metabolismo , Dieta , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/administração & dosagem , Fibrinolíticos/administração & dosagem , Hemostasia/efeitos dos fármacos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombose/tratamento farmacológico
7.
Klin Lab Diagn ; 66(1): 35-41, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33567171

RESUMO

Platelet function testing is widely used to diagnose disorders of the cellular link of hemostasis. The study of platelet aggregation activity is relevant for the prevention of thromboembolic complications in atrial fibrillation and monitoring the effectiveness and safety of therapy. In this study, a comparative analysis of spontaneous and stimulated platelet aggregation in groups of patients with two types of atrial fibrillation was performed - paroxysmal and persistent. The effect of ß-adrenoblocker therapy on platelet aggregation activity in patients with atrial fibrillation was also studied. Platelet aggregation activity was studied using the method of G. Born in the modification of Z.A. Gabbasov on a two-channel laser analyzer "Biola". Collagen at a concentration of 2 mg / ml and adrenaline in a concentration range of 2.5-10 µg / ml were used as aggregation-promoting agents. It has been established that spontaneous aggregation potential and collagen-induced platelet aggregation depend on the type of atrial fibrillation, as well as on the presence or absence of ß-blockers in therapy. The response of platelets to stimulation with adrenaline depends, first of all, on the type of atrial fibrillation and the concentration of adrenaline in the reaction medium. The most significant changes were noted in the group of patients with a paroxysmal form atrial fibrillation, taking ß-blockers in therapy.


Assuntos
Fibrilação Atrial , Fibrilação Atrial/tratamento farmacológico , Plaquetas , Hemostasia , Humanos , Agregação Plaquetária , Testes de Função Plaquetária
8.
Molecules ; 26(4)2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33562030

RESUMO

Coagulation disorders, endotheliopathy and inflammation are the most common hallmarks in SARS-CoV-2 infection, largely determining COVID-19's outcome and severity. Dysfunctions of endothelial cells and platelets are tightly linked in contributing to the systemic inflammatory response that appears to be both a cause and a consequence of COVID-19-associated coagulation disorders and thrombotic events. Indeed, elevated levels of circulating inflammatory cytokines are often associated with abnormal coagulation parameters in COVID-19 patients. Although treatments with low molecular weight heparin (LMWH) have shown beneficial effects in decreasing patient mortality with severe COVID-19, additional therapeutic strategies are urgently needed. Utilizing the anti-inflammatory and anti-thrombotic properties of natural compounds may provide alternative therapeutic approaches to prevent or reduce the risk factors associated with pre-existing conditions and comorbidities that can worsen COVID-19 patients' outcomes. In this regard, resveratrol, a natural compound found in several plants and fruits such as grapes, blueberries and cranberries, may represent a promising coadjuvant for the prevention and treatment of COVID-19. By virtue of its anti-thrombotic and anti-inflammatory properties, resveratrol would be expected to lower COVID-19-associated mortality, which is well known to be increased by thrombosis and inflammation. This review analyzes and discusses resveratrol's ability to modulate vascular hemostasis at different levels targeting both primary hemostasis (interfering with platelet activation and aggregation) and secondary hemostasis (modulating factors involved in coagulation cascade).


Assuntos
/tratamento farmacológico , Hemostasia/efeitos dos fármacos , Resveratrol/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Fibrinolíticos/uso terapêutico , Transtornos Hemostáticos/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Trombose/tratamento farmacológico
10.
PLoS Biol ; 19(2): e3001109, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33596198

RESUMO

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected over 30 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Therefore, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and nonsevere COVID-19. An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with nonsevere disease (not requiring intensive care), general medical in-patients without COVID-19, and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. We demonstrated that routine clinical blood parameters including increased mean platelet volume (MPV) and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit (ICU) admission. Strikingly, agonist-induced ADP release was 30- to 90-fold higher in COVID-19 patients compared with hospitalised controls and circulating levels of platelet factor 4 (PF4), soluble P-selectin (sP-selectin), and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and nonsevere COVID-19. Moreover, we have determined all COVID-19 patients possess hyperactive circulating platelets. These data suggest abnormal platelet reactivity may contribute to hypercoagulability in COVID-19 and confirms the role that platelets/clotting has in determining the severity of the disease and the complexity of the recovery path.


Assuntos
Plaquetas/virologia , /sangue , Trifosfato de Adenosina/metabolismo , Idoso , Coagulação Sanguínea , Plaquetas/citologia , Ensaio de Imunoadsorção Enzimática , Feminino , Hemostasia , Humanos , Inflamação , Unidades de Terapia Intensiva , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Selectina-P/sangue , Fenótipo , Fator Plaquetário 4/sangue , Testes de Função Plaquetária , Trombopoetina/sangue
11.
BMC Neurol ; 21(1): 36, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499823

RESUMO

BACKGROUND: Hemorrhagic transformation (HT) is a serious neurological complication of acute ischemic stroke (AIS) after revascularization. The majority of AIS patients do not have atrial fibrillation (AF) which could also develop into HT. In this study, we aimed to explore whether hemostasis parameters are risk factors of HT in non-AF patients. METHODS: We consecutively enrolled 285 AIS patients with HT. Meanwhile, age- and sex-matched 285 AIS patients without HT were included. The diagnosis of HT was determined by brain CT or MRI during hospitalization. All patients were divided into two subgroups based on the presence of AF and explore the differences between the two subgroups. Blood samples were obtained within 24 h of admission, and all patients were evenly classified into three tertiles according to platelet counts (PLT) levels. RESULTS: In this study, we found the first PLT tertile (OR = 3.509, 95%CI = 1.268-9.711, P = 0.016) was independently associated with HT in non-AF patients, taking the third tertile as a reference. Meanwhile, we also found mean platelet volume (MPV) (OR = 0.605, 95%CI = 0.455-0.805, P = 0.001) and fibrinogen (FIB) (OR = 1.928, 95%CI = 1.346-2.760, P < 0.001) were significantly associated with HT in non-AF patients. But in AF patients, hemostasis parameters showed no significant difference. Meanwhile, we found the MPV (OR = 1.314, 95%CI = 1.032-1.675, P = 0.027) and FIB (OR = 1.298, 95%CI = 1.047-1.610, P = 0.018) were significantly associated with long-term outcomes in non-AF HT patients. CONCLUSIONS: Low PLT, low MPV, and high FIB levels were independently associated with HT in non-AF patients. Additionally, MPV and FIB levels were significantly associated with unfavorable long-term outcomes in non-AF HT patients. Our study showed that hemostasis functions at admission may be beneficial for clinicians to recognize patients with a high risk of HT at an early stage and improve unfavorable long-term outcomes in non-AF patients.


Assuntos
Hemorragia Cerebral/sangue , Hemorragia Cerebral/etiologia , Hemostasia/fisiologia , /complicações , Idoso , Fibrilação Atrial , Estudos de Casos e Controles , Feminino , Fibrinogênio , Humanos , Imagem por Ressonância Magnética , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Fatores de Risco
12.
Int J Mol Sci ; 22(2)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466873

RESUMO

Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary complication in patients with hematologic malignancies or systemic autoimmune disorders. Pathologic findings show pulmonary capillaritis, bland hemorrhage, diffuse alveolar damage, and hemosiderin-laden macrophages, but in the majority of cases, pathogenesis remains unclear. Despite the severity and high mortality, the current treatment options for DAH remain empirical. Systemic treatment to control inflammatory activity including high-dose corticosteroids, cyclophosphamide, and rituximab and supportive care have been applied, but largely unsuccessful in critical cases. Activated recombinant factor VII (FVIIa) can achieve rapid local hemostasis and has been administered either systemically or intrapulmonary for the treatment of DAH. However, there is no randomized controlled study to evaluate the efficacy and safety, and the use of FVIIa for DAH remains open to debate. This review discusses the pathogenesis, diverse etiologies causing DAH, diagnosis, and treatments focusing on hemostasis using FVIIa. In addition, the risks and benefits of the off-label use of FVIIa in pediatric patients will be discussed in detail.


Assuntos
Hemorragia/tratamento farmacológico , Hemostasia/efeitos dos fármacos , Inflamação/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Alvéolos Pulmonares/efeitos dos fármacos , Corticosteroides/uso terapêutico , Ciclofosfamida/uso terapêutico , Fator VIIa/uso terapêutico , Hemorragia/diagnóstico , Hemorragia/etiologia , Humanos , Inflamação/diagnóstico , Pneumopatias/diagnóstico , Pneumopatias/etiologia , Alvéolos Pulmonares/patologia , Proteínas Recombinantes/uso terapêutico , Rituximab/uso terapêutico
13.
Am J Physiol Cell Physiol ; 320(3): C365-C374, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33471623

RESUMO

Factor XI (FXI) has been shown to bind platelets, but the functional significance of this observation remains unknown. Platelets are essential for hemostasis and play a critical role in thrombosis, whereas FXI is not essential for hemostasis but promotes thrombosis. An apparent functional contradiction, platelets are known to support thrombin generation, yet platelet granules release protease inhibitors, including those of activated FXI (FXIa). We aim to investigate the secretory and binding mechanisms by which platelets could support or inhibit FXIa activity. The presence of platelets enhanced FXIa activity in a purified system and increased coagulation Factor IX (FIX) activation by FXIa and fibrin generation in human plasma. In contrast, platelets reduced the activation of FXI by activated coagulation factor XII (FXIIa) and the activation of FXII by kallikrein (PKa). Incubation of FXIa with the platelet secretome, which contains FXIa inhibitors, such as protease nexin-II, abolished FXIa activity, yet in the presence of activated platelets, the secretome was not able to block the activity of FXIa. FXIa variants lacking the anion-binding sites did not alter the effect of platelets on FXIa activity or interaction. Western blot analysis of bound FXIa [by FXIa-platelet membrane immunoprecipitation] showed that the interaction with platelets is zinc dependent and, unlike FXI binding to platelets, not dependent on glycoprotein Ib. FXIa binding to the platelet membrane increases its capacity to activate FIX in plasma likely by protecting it from inhibition by inhibitors secreted by activated platelets. Our findings suggest that an interaction of FXIa with the platelet surface may induce an allosteric modulation of FXIa.


Assuntos
Plaquetas/metabolismo , Fator XIa/metabolismo , Adolescente , Precursor de Proteína beta-Amiloide/metabolismo , Sítios de Ligação/fisiologia , Coagulação Sanguínea/fisiologia , Feminino , Hemostasia/fisiologia , Humanos , Masculino , Trombina/metabolismo , Trombose/metabolismo
14.
J Stroke Cerebrovasc Dis ; 30(3): 105592, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33454647

RESUMO

BACKGROUND: Potential causes of embolic stroke of undetermined source (ESUS) include occult malignancy, venous thrombosis (VTE) with paradoxical embolism, and hypercoagulable disorders. Given the association of markers of coagulation and hemostatic activation (MOCHA) with these causes, the objective of this study was to validate the utility of the MOCHA profile in identifying the underlying cause of stroke. METHODS: We prospectively identified ESUS patients from January 1, 2017 to December 1, 2019 who underwent MOCHA profile (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer) testing. Abnormal MOCHA profile was defined as ≥ 2 abnormal markers. New diagnoses of malignancy, VTE, hypercoagulable disorders and recurrent stroke were identified during routine clinical follow-up. RESULTS: Of 236 ESUS patients, 104 (44%) patients had an abnormal MOCHA profile. In multivariable analyses the number of MOCHA abnormalities was significantly associated with malignancy, VTE, and hypercoagulable disorders (OR 2.59, CI 95% 1.78-3.76, p<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value of an abnormal MOCHA profile for the combined outcome of malignancy, VTE, and hypercoagulability was 96%, 62%, 23%, and 99% respectively. DISCUSSION: The MOCHA profile was able to identify ESUS patients more likely to have malignancy, VTE, and hypercoagulable disorders during follow-up. Our results show that a normal MOCHA profile in ESUS patients can effectively rule out these potential causes of ESUS.


Assuntos
/etiologia , Indicadores Básicos de Saúde , Hemostasia , Neoplasias/diagnóstico , Trombofilia/diagnóstico , Tromboembolia Venosa/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Coagulação Sanguínea , /diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/complicações , Valor Preditivo dos Testes , Recidiva , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombofilia/sangue , Trombofilia/complicações , Tromboembolia Venosa/sangue , Tromboembolia Venosa/complicações
15.
Food Chem Toxicol ; 148: 111974, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33421462

RESUMO

The coronavirus disease (COVID)-19 pandemic is a major challenge for the health systems worldwide. Acute respiratory distress syndrome (ARDS), is one of the most common complications of the COVID-19 infection. The activation of the coagulation system plays an important role in the pathogenesis of ARDS. The development of lung coagulopathy involves thrombin generation and fibrinolysis inhibition. Unfractionated heparin and its recently introduced counterpart low molecular weight heparin (LMWH), are widely used anticoagulants with a variety of clinical indications allowing for limited and manageable physio-toxicologic side effects while the use of protamine sulfate, heparin's effective antidote, has made their use even safer. Tissue-type plasminogen activator (tPA) is approved as intravenous thrombolytic treatment. The present narrative review discusses the use of heparin and tPA in the treatment of COVID-19-induced ARDS and their related potential physio-toxicologic side effects. The article is a quick review of articles on anticoagulation in COVID infection and the potential toxicologic reactions associated with these drugs.


Assuntos
/fisiopatologia , Hemostasia/efeitos dos fármacos , Heparina/uso terapêutico , Trombose/complicações , Ativador de Plasminogênio Tecidual/uso terapêutico , Heparina/farmacologia , Humanos , Ativador de Plasminogênio Tecidual/farmacologia
17.
Arterioscler Thromb Vasc Biol ; 41(3): 999-1011, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33441027

RESUMO

Platelets rapidly undergo responsive transitions in form and function to repair vascular endothelium and mediate hemostasis. In contrast, heterogeneous platelet subpopulations with a range of primed or refractory phenotypes gradually arise in chronic inflammatory and other conditions in a manner that may indicate or support disease. Qualitatively distinguishable platelet phenotypes are increasingly associated with a variety of physiological and pathological circumstances; however, the origins and significance of platelet phenotypic variation remain unclear and conceptually vague. As changes in platelet function in disease exhibit many similarities to platelets following the activation of platelet agonist receptors, the intracellular responses of platelets common to hemostasis and inflammation may provide insights to the molecular basis of platelet phenotype. Here, we review concepts around how protein-level relations-from platelet receptors through intracellular signaling events-may help to define platelet phenotypes in inflammation, immune responses, aging, and other conditions. We further discuss how representing systems-wide platelet proteomics data profiles as circuit-like networks of causally related intracellular events, or, pathway maps, may inform molecular definitions of platelet phenotype. In addition to offering insights into platelets as druggable targets, maps of causally arranged intracellular relations underlying platelet function can also advance precision and interceptive medicine efforts by leveraging platelets as accessible, dynamic, endogenous, circulating biomarkers of vascular wellness and disease. Graphic Abstract: A graphic abstract is available for this article.


Assuntos
Plaquetas/fisiologia , Proteoma/fisiologia , Doenças Vasculares/sangue , Animais , Biomarcadores/sangue , Endotélio Vascular/fisiologia , Hemostasia/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Modelos Cardiovasculares , Fenótipo , Proteômica , Transdução de Sinais , Doenças Vasculares/fisiopatologia
18.
Phytomedicine ; 80: 153363, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33070081

RESUMO

BACKGROUND: The ingestion of flavonoids has been reported to be associated with reduced cardiovascular disease risk. Quercitrin is a common flavonoid in nature, and it exhibits antioxidant properties. Although the process of thrombogenesis is intimately related to cardiovascular disease risk, it is unclear whether quercitrin plays a role in thrombogenesis. PURPOSE: The aim of this study was to examine the antiplatelet effect of quercitrin in platelet activation. METHODS: Platelet aggregation, granule secretion, calcium mobilization, and integrin activation were used to assess the antiplatelet activity of quercitrin. Antithrombotic effect was determined in mouse using ferric chloride (FeCl3)-induced arterial thrombus formation in vivo and thrombus formation on collagen-coated surfaces under arteriolar shear in vitro. Transection tail bleeding time was used to evaluate whether quercitrin inhibited primary hemostasis. RESULTS: Quercitrin significantly impaired collagen-related peptide-induced platelet aggregation, granule secretion, reactive oxygen species generation, and intracellular calcium mobilization. Outside-in signaling of αIIbß3 integrin was significantly inhibited by quercitrin in a concentration-dependent manner. The inhibitory effect of quercitrin resulted from inhibition of the glycoprotein VI-mediated platelet signal transduction during cell activation. Further, the antioxidant effect is derived from decreased phosphorylation of components of the TNF receptor-associated factor 4/p47phox/Hic5 axis signalosome. Oral administration of quercitrin efficiently blocked FeCl3-induced arterial thrombus formation in vivo and thrombus formation on collagen-coated surfaces under arteriolar shear in vitro, without prolonging bleeding time. Studies using a mouse model of ischemia/reperfusion-induced stroke indicated that treatment with quercitrin reduced the infarct volume in stroke. CONCLUSIONS: Our results demonstrated that quercitrin could be an effective therapeutic agent for the treatment of thrombotic diseases.


Assuntos
Fibrinolíticos/farmacologia , Hemostasia/efeitos dos fármacos , Quercetina/análogos & derivados , Trombose/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Animais , Artérias , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/farmacologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Quercetina/efeitos adversos , Quercetina/farmacologia , Traumatismo por Reperfusão/induzido quimicamente , Trombose/induzido quimicamente , Trombose/metabolismo
19.
J Surg Res ; 257: 203-212, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32858321

RESUMO

BACKGROUND: Hibernating American black bears have significantly different clotting parameters than their summer active counterparts, affording them protection against venous thromboembolism during prolonged periods of immobility. We sought to evaluate if significant differences exist between the expression of microRNAs in the plasma of hibernating black bears compared with their summer active counterparts, potentially contributing to differences in hemostasis during hibernation. MATERIALS AND METHODS: MicroRNA sequencing was assessed in plasma from 21 American black bears in summer active (n = 11) and hibernating states (n = 10), and microRNA signatures during hibernating and active state were established using both bear and human genome. MicroRNA targets were predicted using messenger RNA (mRNA) transcripts from black bear kidney cells. In vitro studies were performed to confirm the relationship between identified microRNAs and mRNA expression, using artificial microRNA and human liver cells. RESULTS: Using the bear genome, we identified 15 microRNAs differentially expressed in the plasma of hibernating black bears. Of these microRNAs, three were significantly downregulated (miR-141-3p, miR-200a-3p, and miR-200c-3p), were predicted to target SERPINC1, the gene for antithrombin, and demonstrated regulatory control of the gene mRNA expression in cell studies. CONCLUSIONS: Our findings suggest that the hibernating black bears' ability to maintain hemostasis and achieve protection from venous thromboembolism during prolonged periods of immobility may be due to changes in microRNA signatures and possible upregulation of antithrombin expression.


Assuntos
Hemostasia/genética , Hibernação/genética , MicroRNAs/metabolismo , Ursidae/genética , Tromboembolia Venosa/genética , Animais , Antitrombina III/genética , Linhagem Celular Tumoral , Feminino , Inativação Gênica , Hepatócitos , Humanos , Masculino , MicroRNAs/sangue , Estações do Ano , Regulação para Cima , Ursidae/sangue , Tromboembolia Venosa/prevenção & controle
20.
Methods Mol Biol ; 2217: 237-249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33215384

RESUMO

Platelets are small, anucleate cells that play oversized roles in hemostasis, immunity, and inflammation. An important mediator of platelet function is integrin αIIbß3, which is required for fibrinogen-dependent platelet aggregation during hemostasis. This platelet response is dependent on conformational changes in the integrin induced by "inside-out" biochemical signals that are triggered by platelet agonists. In turn, fibrinogen binding to αIIbß3 initiates "outside-in" biochemical and mechanical signals that regulate the platelet cytoskeleton and help to promote full platelet aggregation and secretory responses. Without a nucleus, there is a limited range of experimental manipulations that are possible with human platelets to study the molecular basis of integrin signaling in these primary cells. Consequently, many studies of αIIbß3 function use genetic approaches that rely on heterologous expression systems or platelets from gene-targeted mice, sometimes with uncertain applicability to human platelets. This chapter will detail a method for genetic manipulation of megakaryocytes and platelets derived from human induced pluripotent stem cells for molecular studies of αIIbß3 signaling and for modeling of human platelet functions potentially relevant to hemostasis, immunity, and inflammation.


Assuntos
Plaquetas/metabolismo , Engenharia Celular/métodos , Megacariócitos/metabolismo , Agregação Plaquetária/genética , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/genética , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Glicoproteína IIb da Membrana de Plaquetas/genética , Plaquetas/citologia , Diferenciação Celular , Linhagem Celular , Citoesqueleto/metabolismo , Citoesqueleto/ultraestrutura , Fibrinogênio/genética , Fibrinogênio/metabolismo , Regulação da Expressão Gênica , Hemostasia/genética , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Megacariócitos/citologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Glicoproteína IIb da Membrana de Plaquetas/metabolismo , Ligação Proteica , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Ubiquitinas/antagonistas & inibidores , Ubiquitinas/genética , Ubiquitinas/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...