Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 400
Filtrar
1.
Arterioscler Thromb Vasc Biol ; 41(11): 2681-2692, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34496636

RESUMO

The immunoglobulin receptor GPVI (glycoprotein VI) is selectively expressed on megakaryocytes and platelets and is currently recognized as a receptor for not only collagen but also a variety of plasma and vascular proteins, including fibrin, fibrinogen, laminin, fibronectin, and galectin-3. Deficiency of GPVI is protective in mouse models of experimental thrombosis, pulmonary thromboembolism as well as in thromboinflammation, suggesting a role of GPVI in arterial and venous thrombus formation. In humans, platelet GPVI deficiency is associated with a mild bleeding phenotype, whereas a common variant rs1613662 in the GP6 gene is considered a risk factor for venous thromboembolism. However, preclinical studies on the inhibition of GPVI-ligand interactions are focused on arterial thrombotic complications. In this review we discuss the emerging evidence for GPVI in venous thrombus formation and leukocyte-dependent thromboinflammation, extending to venous thromboembolism, pulmonary thromboembolism, and cancer metastasis. We also recapitulate indications for circulating soluble GPVI as a biomarker of thrombosis-related complications. Collectively, we conclude that the current evidence suggests that platelet GPVI is also a suitable cotarget in the prevention of venous thrombosis due to its role in thrombus consolidation and platelet-leukocyte complex formation.


Assuntos
Coagulação Sanguínea , Plaquetas/metabolismo , Inflamação/metabolismo , Ativação Plaquetária , Glicoproteínas da Membrana de Plaquetas/metabolismo , Tromboembolia Venosa/metabolismo , Trombose Venosa/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Fibrinolíticos/uso terapêutico , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/patologia , Mediadores da Inflamação/sangue , Ligantes , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Glicoproteínas da Membrana de Plaquetas/antagonistas & inibidores , Transdução de Sinais , Tromboembolia Venosa/sangue , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/patologia , Trombose Venosa/sangue , Trombose Venosa/tratamento farmacológico , Trombose Venosa/patologia
2.
Stroke ; 52(11): e706-e709, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34428931
3.
Biomater Sci ; 9(16): 5612-5625, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34254062

RESUMO

This study reports that the use of low-frequency sonophoresis (LFS) in combination with sponge Haliclona sp. spicules (SHS), referred to as cSoSp (combined Sonophoresis and Spicules), can enhance the transdermal drug delivery in a synergistic manner. The topical application of cSoSp in vitro significantly enhanced the skin absorption of Fluorescent-Dextrans (4000 Da, FD-4K), a model drug of low-molecular-weight heparin (LMWH). The utilization of cSoSp dramatically increased the transdermal flux of FD-4K (188.6 ± 93.7 ng cm-2 h-1) compared to LFS (5.8 ± 3.1 ng cm-2 h-1) and SHS (3.2 ± 1.2 ng cm-2 h-1) among others. The mechanism of action of cSoSp could be attributed to the synergism between plenty of long-lasting nano-channels created by SHS and the disorders of SC lipids made by shock waves of LFS, which improves the homogeneity of the cavitation effects. Furthermore, LMWH (3000 Da) was transdermally delivered by using cSoSp to treat both superficial venous thrombosis (SVT) and deep venous thrombosis (DVT) in the marginal ear vein of rabbits with a good therapeutic effect. Furthermore, skin irritation and toxicity studies using guinea pigs indicated that cSoSp was nonirritating without any morphological changes in the keratinocytes. cSoSp offers a promising strategy to enhance the transdermal delivery of hydrophilic macromolecules such as heparin.


Assuntos
Heparina , Trombose Venosa , Administração Cutânea , Animais , Cobaias , Heparina/metabolismo , Heparina de Baixo Peso Molecular , Coelhos , Pele/metabolismo , Absorção Cutânea , Trombose Venosa/tratamento farmacológico , Trombose Venosa/metabolismo
4.
PLoS One ; 16(5): e0251269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33983979

RESUMO

BACKGROUND: Upper extremity venous thrombosis (UEVT) represents about 10% of venous thrombo-embolic disease. This is mainly explained by the increasing use of central venous line, for oncologic or nutritional care. The factors associated with venous recanalization are not known. OBJECTIVE: The aim of this study was to investigate prognosis factor associated with venous recanalization after UEVT. METHODS: This study included patients with UEVT diagnosed with duplex ultra-sonography (DUS) from January 2015 to December 2017 with DUS evaluations during follow-up. A multivariate Cox proportional-hazards-model analysis was performed to identify predictive factors of UEVT complete recanalization. RESULTS: This study included 494 UEVT, 304 proximal UEVT and 190 distal UEVT. The median age was 58 years, 39.5% were women. Clinical context was: hematological malignancy (40.7%), solid cancer (14.2%), infectious or inflammatory context (49.9%) and presence of venous catheters or pacemaker leads in 86.4%. The rate of recanalization without sequelae of UEVT was 38%. For all UEVT, in multivariate analysis, factors associated with complete vein recanalization were: thrombosis associated with central venous catheter (CVC) (HR:2.40, [1.45;3.95], p<0.001), UEVT limited to a venous segment (HR:1.94, [1.26;3.00], p = 0.003), occlusive thrombosis (HR:0.48 [0.34;0.67], p<0.0001), the presence of a PICC Line (HR:2.29, [1.48;3.52], p<0.001), a thrombosis of deep and distal topography (HR:1.70, [1.10;2.63], p = 0.02) or superficial thrombosis of the forearm (HR:2.79, [1.52;5.12], p<0.001). For deep and proximal UEVT, non-occlusive UEVT (HR:2.23, [1.49;3.33], p<0.0001), thrombosis associated with CVC (HR:1.58, [1.01;2.47], p = 0.04) and infectious or inflammatory context (HR:1.63, [1.10;2.41], p = 0.01) were factors associated with complete vein recanalization. CONCLUSION: In this study, factors associated with UEVT recanalization were UEVT limited to a venous segment, thrombosis associated with CVC, a thrombosis of deep and distal thrombosis topography and superficial thrombosis of the forearm. Occlusive thrombosis was associated with the absence of UEVT recanalization.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Extremidade Superior/irrigação sanguínea , Trombose Venosa/fisiopatologia , Adulto , Idoso , Cateterismo Venoso Central/métodos , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/métodos , Cateteres de Demora/efeitos adversos , Cateteres Venosos Centrais , Feminino , França , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombose , Veias , Trombose Venosa/metabolismo , Trombose Venosa/terapia
5.
Int J Mol Sci ; 22(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33805059

RESUMO

Pancreatic cancer patients have an elevated risk of suffering from venous thrombosis. Among several risk factors that contribute to hypercoagulability of this malignancy, platelets possess a key role in the initiation of clot formation. Although single mechanisms of platelet activation are well-known in principle, combinations thereof and their potential synergy to mediate platelet activation is, in the case of pancreatic cancer, far from being clear. Applying an inhibitor screening approach using light transmission aggregometry, dense granule release, and thrombin formation assays, we provide evidence that a combination of tissue factor-induced thrombin formation by cancer cells and their platelet P-selectin binding is responsible for AsPC-1 and Capan-2 pancreatic cancer cell-mediated platelet activation. While the blockade of one of these pathways leads to a pronounced inhibition of platelet aggregation and dense granule release, the simultaneous blockade of both pathways is inevitable to prevent platelet aggregation completely and minimize ATP release. In contrast, MIA PaCa-2 pancreatic cancer cells express reduced levels of tissue factor and P-selectin ligands and thus turn out to be poor platelet activators. Consequently, a simultaneous blockade of thrombin and P-selectin binding seems to be a powerful approach, as mediated by heparin to crucially reduce the hypercoagulable state of pancreatic cancer patients.


Assuntos
Selectina-P/química , Neoplasias Pancreáticas/metabolismo , Ativação Plaquetária , Trombina/química , Trombose Venosa/metabolismo , Plaquetas/metabolismo , Linhagem Celular Tumoral , Humanos , Ligantes , Adesividade Plaquetária , Agregação Plaquetária , Fatores de Risco , Trombofilia , Tromboplastina/metabolismo , Trombose Venosa/complicações
6.
Bioengineered ; 12(1): 1360-1368, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33896376

RESUMO

This study is aimed at identifying the roles of AGE/RAGE and ET-1 in deep vein thrombosis (DVT). Advanced glycation end products (AGEs) in glycated human serum albumin (M-HSA) were detected by ELISA. The viability of HUVECs was examined by CCK-8 assay. Flow cytometry was performed to detect cell apoptosis, followed by ELISA for the detection of inflammatory cytokine level and oxidative stress level in HUVECs. Immunofluorescence was performed to detect ET-1 and eNOS expression. The expression of specific proteins was assayed by western blot. As a result, decreased HUVEC viability was observed after stimulation with M-HSA, whereas RAGE inhibitor improved it. Cell apoptosis showed the opposite trend. Additionally, M-HSA-induced inflammatory cytokine release and oxidative stress of HUVECs were both alleviated by RAGE inhibitor. RAGE inhibitor also increased the levels of NO and eNOS while decreasing the level of ET-1 in M-HSA-stimulated HUVECs. Furthermore, decreased protein expression of Bax, cleaved-caspase3, RAGE, p65, ET-1 and iNOS was observed after treatment with RAGE inhibitor, in addition to increased protein expression of Bcl-2 and eNOS. In conclusion, blocking AGE/RAGE pathway downregulates ET-1, thereby mitigating HUVEC damage in DVT.


Assuntos
Antígenos de Neoplasias/metabolismo , Regulação para Baixo , Endotelina-1/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Trombose Venosa/metabolismo , Caspase 3/metabolismo , Sobrevivência Celular , Glicosilação , Humanos , Inflamação/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Albumina Sérica/metabolismo , Proteína X Associada a bcl-2/metabolismo
7.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799528

RESUMO

Obstructive sleep apnoea (OSA) is a common disease which is characterised by repetitive collapse of the upper airways during sleep resulting in chronic intermittent hypoxaemia and frequent microarousals, consequently leading to sympathetic overflow, enhanced oxidative stress, systemic inflammation, and metabolic disturbances. OSA is associated with increased risk for cardiovascular morbidity and mortality, and accelerated coagulation, platelet activation, and impaired fibrinolysis serve the link between OSA and cardiovascular disease. In this article we briefly describe physiological coagulation and fibrinolysis focusing on processes which could be altered in OSA. Then, we discuss how OSA-associated disturbances, such as hypoxaemia, sympathetic system activation, and systemic inflammation, affect these processes. Finally, we critically review the literature on OSA-related changes in markers of coagulation and fibrinolysis, discuss potential reasons for discrepancies, and comment on the clinical implications and future research needs.


Assuntos
Síndrome Coronariana Aguda/metabolismo , Fibrinólise/genética , Hipóxia/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Acidente Vascular Cerebral/metabolismo , Trombose Venosa/metabolismo , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/fisiopatologia , Fatores de Coagulação Sanguínea/genética , Fatores de Coagulação Sanguínea/metabolismo , Plaquetas/metabolismo , Plaquetas/patologia , Fibrinogênio/genética , Fibrinogênio/metabolismo , Regulação da Expressão Gênica , Humanos , Hipóxia/complicações , Hipóxia/genética , Hipóxia/fisiopatologia , Inflamação , Estresse Oxidativo , Ativação Plaquetária/genética , Agregação Plaquetária/genética , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/genética , Apneia Obstrutiva do Sono/fisiopatologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/fisiopatologia , Trombose Venosa/complicações , Trombose Venosa/genética , Trombose Venosa/fisiopatologia
8.
Int J Mol Sci ; 22(8)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917767

RESUMO

Venous thromboembolism, a complex disease combining deep vein thrombosis (DVT) and its most dangerous complication, pulmonary embolism (PE), strikes millions of people worldwide [...].


Assuntos
Trombose Venosa/diagnóstico , Trombose Venosa/etiologia , Biomarcadores , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Trombose Venosa/metabolismo , Trombose Venosa/terapia
9.
Pediatr Hematol Oncol ; 38(6): 528-542, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33646916

RESUMO

Effective treatment for acute, extensive, symptomatic lower extremity (LE) thrombosis involves thrombolysis in addition to anticoagulation. There is limited available data on the outcomes and safety of thrombolysis to help guide its use in pediatrics and young adults. A retrospective study of children and young adults (<21 years of age) that received catheter directed thrombolysis (CDT) for LE and inferior vena cava (IVC) thrombosis was performed over a 5-year span at a pediatric tertiary care center. A total of 29 patients were identified for inclusion in the study, 76% (n = 22) received overnight CDT while 24% (n = 7) received tissue plasminogen activator as a bolus dose during a single interventional procedure. The median age of the cohort was 15.8 years (range 0-19.1). All patients were treated with a course of therapeutic anticoagulation. The thromboses represented were extensive, with 93% (n = 27) being occlusive and affecting multiple venous segments. Thrombus resolution occurred in 35% (n = 10) of patients. Rivaroxaban use (p < 0.01) during the course of anticoagulation and estrogen-containing hormonal therapy (p = 0.01) use prior to diagnosis were associated with thrombus resolution, while Hispanic ethnicity (p = 0.06) had a trend toward thrombus persistence. There were one major and 3 minor bleeding events that occurred as complications of thrombolysis and no treatment related deaths. This study provides baseline information that can be used to help guide clinicians treating similar patients and suggests the need to develop an improved, uniform treatment approach for superior resolution rates.


Assuntos
Anticoagulantes/administração & dosagem , Extremidade Inferior/irrigação sanguínea , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Veia Cava Inferior/metabolismo , Trombose Venosa/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Veia Cava Inferior/patologia , Trombose Venosa/metabolismo , Adulto Jovem
10.
PLoS One ; 16(3): e0247615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33705460

RESUMO

BACKGROUND: Despite advances in immunosuppression and surgical technique, pancreas transplantation is encumbered with a high rate of complication and graft losses. Particularly, venous graft thrombi occur relatively frequently and are rarely detected before the transplant is irreversibly damaged. METHODS: To detect complications early, when the grafts are potentially salvageable, we placed microdialysis catheters anteriorly and posteriorly to the graft in a cohort of 34 consecutive patients. Glucose, lactate, pyruvate, and glycerol were measured at the bedside every 1-2 hours. RESULTS: Nine patients with graft venous thrombosis had significant lactate and lactate-to-pyruvate-ratio increases without concomitant rise in blood glucose or clinical symptoms. The median lactate in these patients was significantly higher in both catheters compared to non-events (n = 15). Out of the nine thrombi, four grafts underwent successful angiographic extraction, one did not require intervention and four grafts were irreversibly damaged and explanted. Four patients with enteric anastomosis leakages had significantly higher glycerol measurements compared to non-events. As with the venous thrombi, lactate and lactate-to-pyruvate ratio were also increased in six patients with graft surrounding hematomas. CONCLUSIONS: Bedside monitoring with microdialysis catheters is a promising surveillance modality of pancreatic grafts, but differentiating between the various pathologies proves challenging.


Assuntos
Rejeição de Enxerto/diagnóstico , Hematoma/diagnóstico , Microdiálise/métodos , Monitorização Fisiológica/métodos , Transplante de Pâncreas/efeitos adversos , Trombose Venosa/diagnóstico , Adulto , Soro Antilinfocitário/uso terapêutico , Cateteres de Demora , Diagnóstico Precoce , Estudos de Viabilidade , Feminino , Glucose/metabolismo , Glicerol/metabolismo , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Hematoma/etiologia , Hematoma/imunologia , Hematoma/metabolismo , Humanos , Imunossupressores/uso terapêutico , Ácido Láctico/metabolismo , Masculino , Microdiálise/instrumentação , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Ácido Pirúvico/metabolismo , Tacrolimo/uso terapêutico , Trombose Venosa/etiologia , Trombose Venosa/imunologia , Trombose Venosa/metabolismo
11.
Int J Mol Med ; 47(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760144

RESUMO

Deep vein thrombosis (DVT) is a common peripheral vascular disease, which may result in pulmonary embolism and is accompanied by endothelial injury. However, the pathogenesis of DVT remains unclear. Coagulation factor XII (FXII), as an important coagulation factor, has been reported to be closely associated with thrombosis. However, the association between FXII protein and DVT formation is not yet fully understood. The present study examined the effects of FXII protein on DVT formation and aimed to reveal the underlying mechanism. In the present study, histological characterization of the femoral vein tissue was examined by hematoxylin and eosin staining. The damage to the femoral vein tissue was examined by TUNEL assay. Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were examined using ELISA. Tumor necrosis factor (TNF)­α, interleukin (IL)­6, IL­8 and phosphoinositide 3­kinase (PI3K)/AKT signaling were determined by ELISA, immunohistochemical staining and western blot analysis. The results demonstrated that thrombosis, FXII protein, cell apoptosis and the SOD concentrations were decreased, while the MDA concentrations were increased in mice with DVT compared with the control or sham groups. TNF­α, IL­6, IL­8 and PI3K/AKT signaling was also upregulated in the mice with DVT. Furthermore, the knockdown of FXII significantly upregulated the SOD concentrations and downregulated thrombosis and cell apoptosis, as well as the MDA concentrations in mice with DVT. The knockdown of FXII also significantly downregulated the protein expression of TNF­α, IL­6 and IL­8, and the activation of PI3K/AKT signaling. Additionally, LY294002 pre­treatment markedly downregulated thrombosis and cell apoptosis and the MDA content, whereas it upregulated the SOD concentrations in mice with DVT. LY294002 pre­treatment also significantly downregulated the TNF­α, IL­6 and IL­8 protein levels. Taken together, the present study demonstrates that FXII protein promotes DVT via the activation of PI3K/AKT signaling by inducing an inflammatory response. Targeting FXII protein may thus prove to be a potential approach for the treatment of DVT.


Assuntos
Fator XII/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Trombose Venosa/metabolismo , Animais , Citocinas/sangue , Fator XII/genética , Veia Femoral/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais , Trombose Venosa/patologia
12.
Am J Med Sci ; 361(4): 509-516, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33781391

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a frequent and potentially fatal disease, but its pathophysiology is incompletely understood. microRNAs (miR) dysregulate hemostatic proteins and influence thrombotic pathology by posttranscriptional regulation of gene expression. Consensus in defining VTE-related miR clusters and functionally relevant miR has not been reached. We aimed to generate a miR database in patients at high thrombotic risk of VTE and explored their biological functions by seeking information on their messenger RNA targets. METHODS: By high-throughput screening (Affymetrix miRNA Microarray), we identified 159 miR in venous blood of male patients who had two unprovoked VTE and in age-matched male controls. RESULTS: Of the 159 miR, 41 were significantly higher expressed in patients compared to controls. Six miR (hsa-miR-6798-3p, hsa-miR-6789-5p hsa-miR-4651, hsa-miR-6765-5p, hsa-miR-6816-5p, hsa-miR-4734) were modulated ≥ 5.0-fold higher. Higher expression levels of 4 of these miR (hsa-miR-6789-5p, hsa-miR-4651, hsa-miR-6765-5p, and hsa-miR-6816-5p; primers were unavailable for hsa-miR-6798-3p and hsa-miR-4734) were confirmed by quantitative real-time polymerase chain reaction in 10 independent patients and 10 control samples. Ingenuity Pathway Analysis identified 23 altered miR including hsa-miR-6789-5p, hsa-miR-4651, hsa-miR-6765-5p and hsa-miR-4734 as the main regulators of messenger RNAs involved in the pathology of VTE. Seven messenger RNA targets including thrombomodulin and four targets related to platelet function had a direct relationship to 4 identified miR. CONCLUSIONS: We provide evidence of distinct, independently validated miR signatures in patients with VTE and identified a subset of miR as main regulators of messenger RNA involved in disorders related to pathophysiologic processes in venous thrombosis development.


Assuntos
Expressão Gênica , MicroRNAs/metabolismo , Plasma/química , Trombose Venosa/metabolismo , Adulto , Idoso , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade
13.
Blood ; 137(16): 2256-2266, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33556175

RESUMO

Genome-wide association studies linked expression of the human neutrophil antigen 3b (HNA-3b) epitope on the Slc44a2 protein with a 30% decreased risk of venous thrombosis (VT) in humans. Slc44a2 is a ubiquitous transmembrane protein identified as a receptor for von Willebrand factor (VWF). To explain the link between Slc44a2 and VT, we wanted to determine how Slc44a2 expressing either HNA-3a or HNA-3b on neutrophils could modulate their adhesion and activation on VWF under flow. Transfected HEK293T cells or neutrophils homozygous for the HNA-3a- or HNA-3b-coding allele were purified from healthy donors and perfused in flow chambers coated with VWF at venous shear rates (100 s-1). HNA-3a expression was required for Slc44a2-mediated neutrophil adhesion to VWF at 100 s-1. This adhesion could occur independently of ß2 integrin and was enhanced when neutrophils were preactivated with lipopolysaccharide. Moreover, specific shear conditions with high neutrophil concentration could act as a "second hit," inducing the formation of neutrophil extracellular traps. Neutrophil mobilization was also measured by intravital microscopy in venules from SLC44A2-knockout and wild-type mice after histamine-induced endothelial degranulation. Mice lacking Slc44a2 showed a massive reduction in neutrophil recruitment in inflamed mesenteric venules. Our results show that Slc44a2/HNA-3a is important for the adhesion and activation of neutrophils in veins under inflammation and when submitted to specific shears. The fact that neutrophils expressing Slc44a2/HNA-3b have a different response on VWF in the conditions tested could thus explain the association between HNA-3b and a reduced risk for VT in humans.


Assuntos
Isoantígenos/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Neutrófilos/citologia , Fator de von Willebrand/metabolismo , Animais , Circulação Sanguínea , Adesão Celular , Células Cultivadas , Armadilhas Extracelulares/genética , Armadilhas Extracelulares/metabolismo , Expressão Gênica , Células HEK293 , Humanos , Isoantígenos/genética , Masculino , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Trombose Venosa/genética , Trombose Venosa/metabolismo
14.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540604

RESUMO

Diseases such as myocardial infarction, ischaemic stroke, peripheral vascular disease and venous thromboembolism are major contributors to morbidity and mortality. Procoagulant, anticoagulant and fibrinolytic pathways are finely regulated in healthy individuals and dysregulated procoagulant, anticoagulant and fibrinolytic pathways lead to arterial and venous thrombosis. In this review article, we discuss the (patho)physiological role and laboratory assessment of fibrin, factor XIII and endogenous fibrinolysis, which are key players in the terminal phase of the coagulation cascade and fibrinolysis. Finally, we present the most up-to-date evidence for their involvement in various disease states and assessment of cardiovascular risk.


Assuntos
Fator XIII/fisiologia , Fibrina/fisiologia , Trombose/fisiopatologia , Fator XIII/análise , Fator XIII/metabolismo , Fibrina/análise , Fibrina/metabolismo , Fibrinólise , Humanos , Trombose/sangue , Trombose/metabolismo , Trombose Venosa/sangue , Trombose Venosa/metabolismo , Trombose Venosa/fisiopatologia
15.
Aging (Albany NY) ; 13(5): 6918-6935, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33638947

RESUMO

Aging is associated with the increased incidence of deep venous thrombosis (DVT), resulting in significant morbidity and mortality in the elderly, but the underlying mechanism is elusive. Silent information regulator 1 (Sirt1) is linked to the senescence, inflammation, oxidative stress and platelet adhesion of endothelial cells. Here we showed that DVT was associated with the senescence of endothelium and lower expression of Sirt1. Furthermore, Sirt1 could inhibit endothelial senescence and reduce the occurrence of DVT. Interestingly, we found antisense long non-coding RNA (lncRNA Sirt1-AS) upregulated Sirt1, decreased the expression of senescence and DVT associated biomarkers in human vascular endothelial cells (HUVECs). In addition, lncRNA Sirt1-AS overexpression alleviated DVT through upregulating Sirt1 and thereby inducing Foxo3a degradation. In conclusion, our findings demonstrate that lncRNA Sirt1-AS may be a potential new biomarker for DVT.


Assuntos
Envelhecimento/metabolismo , RNA Longo não Codificante/metabolismo , Sirtuína 1/metabolismo , Trombose Venosa/metabolismo , Animais , Feminino , Citometria de Fluxo , Proteína Forkhead Box O3 , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hibridização in Situ Fluorescente , Masculino , Camundongos , Pessoa de Meia-Idade , Ubiquitinação , Regulação para Cima
16.
Mol Cell Biochem ; 476(3): 1489-1504, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33398665

RESUMO

Integrins are a group of transmembrane glycoprotein receptors that are responsible for platelet activation through bidirectional signalling. These receptors have left their footprints in various cellular events and have intrigued many groups of scientists that have led to some significant discoveries. A lot of the recent understanding of haemostasis has been possible due to the integrins filling the gaps in between several cellular mechanism. Apart from this, other important functions carried out by integrins are growth and maturation of cardiomyocytes, mechano-transduction, and interaction with actin cytoskeleton. The signalling cascade for integrin activation involves certain intracellular interacting proteins, which initiates the step-by-step activation procedure through 'inside-out' signalling. The signalling cascade gets activated through 'outside-in' signalling with the involvement of agonists such as ADP, Fibronectin, Vitronectin, and so on. This is a crucial step for the downstream processes of platelet spreading, followed by aggregation, clot progression and finally thrombus formation. Researchers throughout the world have shown direct relation of integrins with CVD and cardiac remodelling. The present review aims to summarize the information available so far on the involvement of integrins in thrombosis and its relationship to DVT. This information could be a bedrock of hidden answers to several questions on pathogenesis of deep vein thrombosis.


Assuntos
Integrinas/metabolismo , Trombose/metabolismo , Trombose Venosa/metabolismo , Citoesqueleto de Actina/metabolismo , Animais , Plaquetas/metabolismo , Proteínas do Citoesqueleto/metabolismo , Citoesqueleto/metabolismo , Modelos Animais de Doenças , Coração/fisiologia , Hemostasia , Ligantes , Camundongos , Camundongos Transgênicos , Miocárdio/metabolismo , Agregação Plaquetária , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Transdução de Sinais , Talina/metabolismo , Proteínas rap de Ligação ao GTP/metabolismo
17.
Eur Rev Med Pharmacol Sci ; 25(1): 353-361, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33506924

RESUMO

OBJECTIVE: To explore the clinical and prognostic features of CVT caused by PROS1 gene mutations and to provide clinical experience for new oral anticoagulants, such as rivaroxaban, in the treatment of CVT with a high risk of thrombosis. PATIENTS AND METHODS: The CVT patient's clinical symptoms were described, and the brain imaging and blood coagulation tests were performed to confirm the diagnosis of CVT. The patient's family members were recruited to receive blood coagulation tests and ultrasonic examination of lower limb vessels. Genetic analysis on the pedigree was carried out to identify the responsible gene for PS deficiency. We followed-up with this patient for 24 months to evaluate the clinical outcomes, laboratory results and imaging performances of CVT. RESULTS: The patient presented with typical CVT symptoms, including headache and epilepsy. Brain CT showed hemorrhage in the bilateral frontal lobe and left occipital lobe, while MRV demonstrated that thrombus had occurred. It was reviewed that the patient and his mother had a history of bilateral leg deep vein thrombosis. Gene tests revealed that the patient and two family members carried a heterozygous mutation of PROS1 (c.751_752delAT, p.M251Vfs*17). During 24 months of follow-up study, the patient was treated with rivaroxaban continuously and recovered well, supported by an mRS score that remained below 2. Blood coagulation tests were within normal limits, and MRV revealed partial recanalization of the cerebral venous sinus. CONCLUSIONS: The frame shift mutation in the PROS1 gene (c.751_752delAT) may greatly affect the function of protein S and lead to a severe phenotype of CVT. Rivaroxaban showed a satisfying therapeutic effect in this CVT patient with hereditary thrombophilia.


Assuntos
Anticoagulantes/farmacologia , Deficiência de Proteína S/tratamento farmacológico , Proteína S/genética , Rivaroxabana/farmacologia , Trombofilia/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Administração Oral , Adulto , Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Seguimentos , Humanos , Masculino , Mutação , Linhagem , Proteína S/metabolismo , Deficiência de Proteína S/genética , Deficiência de Proteína S/metabolismo , Rivaroxabana/administração & dosagem , Trombofilia/genética , Trombofilia/metabolismo , Trombose Venosa/genética , Trombose Venosa/metabolismo
18.
Blood ; 137(11): 1517-1526, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32932520

RESUMO

The cells and mechanisms involved in blood clot resorption are only partially known. We show that regulatory T cells (Tregs) accumulate in venous blood clots and regulate thrombolysis by controlling the recruitment, differentiation and matrix metalloproteinase (MMP) activity of monocytes. We describe a clot Treg population that forms the matricellular acid- and cysteine-rich protein SPARC (secreted protein acidic and rich in cysteine) and show that SPARC enhances monocyte MMP activity and that SPARC+ Tregs are crucial for blood clot resorption. By comparing different treatment times, we define a therapeutic window of Treg expansion that accelerates clot resorption.


Assuntos
Osteonectina/metabolismo , Linfócitos T Reguladores/metabolismo , Trombose Venosa/metabolismo , Animais , Fibrinólise , Metaloproteinases da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Monócitos/metabolismo , Monócitos/patologia , Linfócitos T Reguladores/patologia , Trombose Venosa/sangue , Trombose Venosa/patologia
19.
J Vasc Surg Venous Lymphat Disord ; 9(3): 770-780.e7, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32860957

RESUMO

OBJECTIVE: Endothelial-derived molecules involved in thrombosis and hemostasis have been investigated mainly in arteries and in experimental animals. The actual presence and integral function of these molecules in the human deep venous system have received less attention. Our aim was to evaluate the expression of certain prothrombotic and antithrombotic genes in the normal human deep veins of the lower extremities. METHODS: Macroscopically intact and competent valve-containing segments of human deep veins were prospectively collected from patients who had undergone above-knee amputation. Vein samples were separated into four zones: zone 1, postvalve (downstream, proximal) vein wall; zone 2, the valve cusp; zone 3, prevalve (upstream, distal) vein wall; and zone 4, vein wall within the valve cusp (cusp removed). Real-time quantitative polymerase chain reaction for principal genes involved in coagulation, fibrinolysis, and inflammation was performed to quantify messenger RNA. Selected protein gene products were measured by the western blot assay. One additional valve-containing segment underwent mass spectrometry analysis to investigate global differences in the proteome between the study zones. RESULTS: Seventeen valve-containing vein segments were analyzed. Significant upregulation of antithrombotic (protein C receptor [PROCR], thrombomodulin [THBD], tissue factor pathway inhibitor [TFPI]), prothrombotic (con Willebrand factor [VWF]), and proinflammatory (selectin P [SELP], intercellular adhesion molecule 1 [ICAM1]) genes was found in the valve cusp compared with the vein wall (P < .05). PROCR and THBD demonstrated the highest level of upregulation in the valve cusp. PROCR, serpin peptidase inhibitor, clade E, member 1 (SERPINE1), and SELP were upregulated in the valve cusp at the protein level (P < .05). Messenger RNA composition in the vein wall within the valve cusp was similar to the prevalve and postvalve vein wall for all genes, except for two times overexpressed ICAM1 (P < .05). Substantial differences within the proteome between the study zones were observed with mass spectrometry. CONCLUSIONS: The biological properties of the valve cusp, vein wall within the valve cusp, and vein wall beyond the valve cusp are different. The endothelium of the valve cusps of a normal competent deep venous valve may be naturally less thrombogenic compared with the vein wall. The endothelium of the valve cusp may have a higher potential to interact with white blood cells compared with the vein wall. Mass spectrometry demonstrates substantial differences in the proteome between the vein wall and the valve cusps that were not anticipated before. (J Vasc Surg Venous Lymphat Disord 2021;9:770-80.) CLINICAL RELEVANCE: Deep vein thrombosis (DVT) is a major cause of mortality, morbidity, and impaired quality of life. Multiple risk factors have been identified, although their relative weight and pathophysiologic interactions remain obscure. Many patients with multiple risk factors for DVT never develop this condition. Conversely, in numerous cases DVT cannot be attributed to any known clinical risk factor. The molecular mechanisms that initiate DVT are unclear. An improved understanding of the normal biology of human deep veins will serve as an important foundation for new hypotheses of the pathogenesis of DVT. The latter may suggest new projects on novel therapeutic strategies.


Assuntos
Extremidade Inferior/irrigação sanguínea , Proteoma , RNA Mensageiro/genética , Transcriptoma , Veias/química , Trombose Venosa/genética , Idoso , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteômica , Reação em Cadeia da Polimerase em Tempo Real , Espectrometria de Massas em Tandem , Veias/patologia , Trombose Venosa/metabolismo , Trombose Venosa/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...