Abstract:
:Epidemiologic studies have correlated elevated plasma fibrinogen (hyperfibrinogenemia) with risk of cardiovascular disease and arterial and venous thrombosis. However, it is unknown whether hyperfibrinogenemia is merely a biomarker of the proinflammatory disease state or is a causative mechanism in the etiology. We raised plasma fibrinogen levels in mice via intravenous infusion and induced thrombosis by ferric chloride application to the carotid artery (high shear) or saphenous vein (lower shear); hyperfibrinogenemia significantly shortened the time to occlusion in both models. Using immunohistochemistry, turbidity, confocal microscopy, and elastometry of clots produced in cell and tissue factor-initiated models of thrombosis, we show that hyperfibrinogenemia increased thrombus fibrin content, promoted faster fibrin formation, and increased fibrin network density, strength, and stability. Hyperfibrinogenemia also increased thrombus resistance to tenecteplase-induced thrombolysis in vivo. These data indicate that hyperfibrinogenemia directly promotes thrombosis and thrombolysis resistance and does so via enhanced fibrin formation and stability. These findings strongly suggest a causative role for hyperfibrinogenemia in acute thrombosis and have significant implications for thrombolytic therapy. Plasma fibrinogen levels may be used to identify patients at risk for thrombosis and inform thrombolytic administration for treating acute thrombosis/thromboembolism.
journal_name
Bloodjournal_title
Bloodauthors
Machlus KR,Cardenas JC,Church FC,Wolberg ASdoi
10.1182/blood-2010-11-316885subject
Has Abstractpub_date
2011-05-05 00:00:00pages
4953-63issue
18eissn
0006-4971issn
1528-0020pii
blood-2010-11-316885journal_volume
117pub_type
杂志文章相关文献
BLOOD文献大全abstract::Hematopoietic stem cells (HSCs) maintain stemness through various mechanisms that protect against stressful conditions. Heat shock proteins (HSPs) preserve cell homeostasis during stress responses through protein quality control, suggesting that HSPs may safeguard HSCs against numerous traumas. Here, we show that mort...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-06-508333
更新日期:2014-01-02 00:00:00
abstract::Bernard-Soulier syndrome (BSS) platelets, which lack the membrane glycoprotein complex Ib-IX, do not adhere to subendothelium. The adhesion of platelets from two patients with BSS to subendothelial microfibrils (MFs) and type I collagen was compared in an in vitro assay adapted to patients with low platelet count. Wit...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::The clinical severity of common hereditary elliptocytosis (HE) is highly variable, ranging from an asymptomatic carrier state to a severe hemolytic anemia. To elucidate the molecular basis of this variable clinical expression, we evaluated 56 subjects from 24 HE kindred, who carry alpha spectrin mutants characterized ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-09-01 00:00:00
abstract::CD4(+) T helper 1 (Th1) cells and Th2 cells are distinguished based on the pattern of cytokines they are able to produce. Selectin ligands and chemokine receptors are differentially expressed in Th1 and Th2 cells, providing a basis for tissue-specific recruitment of helper T-cell subsets. However, the modes and mechan...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00
abstract::Under evolutionary pressure to counter the toxicity of iron and to maintain adequate iron supply for hemoglobin synthesis and essential metabolic functions, humans and other vertebrates have effective mechanisms to conserve iron and to regulate its concentration, storage, and distribution in tissues. The iron-regulato...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2011-01-258467
更新日期:2011-04-28 00:00:00
abstract::DNA amplification combined with hybridization with 32P-labeled synthetic oligonucleotide probes has been used to identify base substitutions in the 5' promoter region of the A gamma globin gene in members of eleven families from China, Sardinia, Canada, and the United States who had a heterozygosity for the A gamma-be...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::Intravital microscopy was used to monitor leukocyte traffic across rat mesenteric postcapillary venules induced by the inactive terminal complement (C) complex (iTCC) topically applied to ileal mesentery. Leukocytes started rolling within 15 minutes from the administration of iTCC, and by 1 hour they adhered almost co...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.1.185
更新日期:2002-01-01 00:00:00
abstract::Tissue-type plasminogen activator (t-PA) is approved for treatment of ischemic stroke patients, but it increases the risk of intracranial bleeding (ICB). Previously, we have shown in a mouse stroke model that stromelysin-1 (matrix metalloproteinase-3 [MMP-3]) induced in endothelial cells was critical for ICB induced b...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-02-203919
更新日期:2009-10-08 00:00:00
abstract::The mechanisms of resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) often remain obscure. Analysis of patient samples during disease progression revealed the up-regulation of the oncogene TWIST-1, also measured in primary samples from TKI-resistant patients. Moreover, we found that TWIS...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-11-254680
更新日期:2011-02-03 00:00:00
abstract::Although the binding of endothelial cell protein C receptor (EPCR) to its ligands is well characterized at the biochemical level, it remains unclear how EPCR interaction with its ligands at the cell surface impacts its cellular trafficking. We characterized the cellular localization and trafficking of EPCR in endothel...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-03-208900
更新日期:2009-08-27 00:00:00
abstract::Dendritic cell (DC) development is efficiently supported by Flt3-ligand or GM-CSF in vitro, and lymphoid-organ DC maintenance in vivo is critically dependent on Flt3-ligand. However, the relevance of GM-CSF for lymphoid-tissue DC maintenance and the importance of both cytokines for nonlymphoid organ DC homeostasis are...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-02-206318
更新日期:2009-07-23 00:00:00
abstract::Monoclonal antibodies were raised after injecting mice with isolated human dense granules. Several of these monoclonals were found to recognize a 40-Kd dense granule membrane protein. Western blot and immunofluorescent analysis confirmed the dense-granule specificity. After thrombin activation, the protein was found i...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::CD4(+)CD25(+)FOXP3(+) regulatory T cells (CD4(+) Treg cells) are thought to differentiate in the thymus and immigrate from the thymus to the periphery. Treg cells can regulate both acquired and innate immunity through multiple modes of suppression. The cross-talk between Treg cells and targeted cells, such as antigen-...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2006-01-0177
更新日期:2006-07-15 00:00:00
abstract::Severe congenital neutropenia as well as primary myelofibrosis are rare in infancy. Elucidation of the underlying mechanism is important because it extends our understanding of the more common adult forms of these disorders. Using homozygosity mapping followed by exome sequencing, we identified a Thr224Asn mutation in...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-12-475566
更新日期:2013-06-20 00:00:00
abstract::The intercellular crosstalk between hematological malignancies and the tumor microenvironment is mediated by cell-to-cell interactions and soluble factors. One component of the secretome that is gaining increasing attention is the extracellular vesicles and, in particular, the exosomes. Apart from the role as vectors ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-05-715961
更新日期:2016-12-08 00:00:00
abstract::Most patients with acute myeloid leukemia (AML) enter complete remission (CR) after treatment with chemotherapy, but a large number of them experience relapse with resistant disease. To identify genes that are associated with their prognoses, we analyzed gene expression in 54 pediatric patients with AML using an oligo...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-02-0578
更新日期:2003-09-01 00:00:00
abstract::Studies have demonstrated that common polymorphisms in Th1 and Th2 cytokine genes can alter gene expression, modulate the balance between Th1/Th2 responsiveness, and influence susceptibility for autoimmune disorders, infectious diseases, and cancer. We analyzed one or more single nucleotide polymorphisms (SNPs) in 20 ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-10-4160
更新日期:2006-05-15 00:00:00
abstract::The canonical role of the hemostatic and fibrinolytic systems is to maintain vascular integrity. Perturbations in either system can prompt primary pathological end points of hemorrhage or thrombosis with vessel occlusion. However, fibrin(ogen) and proteases controlling its deposition and clearance, including (pro)thro...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2018-07-818211
更新日期:2019-02-07 00:00:00
abstract::Antigenic stimulation through the B-cell antigen receptor (BCR) is considered to promote the expansion of chronic lymphocytic leukemia (CLL) B cells. The spleen tyrosine kinase (Syk), a key component of BCR signaling, can be blocked by R406, a small-molecule Syk inhibitor, that displayed activity in CLL patients in a ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-03-212837
更新日期:2009-07-30 00:00:00
abstract::Immunoglobulin class switching from IgM to IgG in response to peptides is generally T cell-dependent and vaccination in T cell-deficient individuals is inefficient. We show that a vaccine consisting of a dense array of peptides on liposomes induced peptide-specific IgG responses totally independent of T-cell help. Ind...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-02-413831
更新日期:2013-01-03 00:00:00
abstract::Umbilical cord blood (UCB) is an attractive cell source for hematopoietic cell transplantation (HCT). Here we examine whether the combination of homeobox B4 (HOXB4) and Delta-1 ligand (DL) synergize when used together. Monkey and human UCB CD34(+) cells were transduced with a HOXB4-expressing gammaretroviral vector an...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-05-286062
更新日期:2010-12-23 00:00:00
abstract::Fas (CD95/Apo-1) mutations were previously reported as the genetic defect responsible for human lymphoproliferative syndrome associated with autoimmune manifestations (also known as autoimmune lymphoproliferative syndrome or Canale-Smith syndrome). We have identified 14 new heterozygous Fas mutations. Analysis of pati...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-10-15 00:00:00
abstract::The mouse Pim-1 gene encodes two cytoplasmic serine-threonine-specific protein kinases. The gene has been found to be activated (overexpressed) by retroviral insertion in hematopoietic tumors in mice. Transgenic mice that overexpress Pim-1 (E mu-Pim-1) have a low incidence of spontaneous T-cell lymphomas and an increa...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::We examined the role of the T-cell antigen CD2 in the regulation of erythropoiesis by the lymphokine cascade. T-cell interleukin-2 (IL-2) receptors (p55) were induced via triggering of the antigen receptor-associated CD3 epitope. Before CD3 triggering T cells were preincubated with a CD2-blocking (Leu-5b) or isotype c...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::Inherited bleeding, thrombotic, and platelet disorders (BPDs) are diseases that affect ∼300 individuals per million births. With the exception of hemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialized tests are usually required to reach a put...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-12-688267
更新日期:2016-06-09 00:00:00
abstract::Surprisingly little is known about the interaction of human blood mononuclear cells with viruses. Here, we show that monocytes are the predominant cell type infected when peripheral blood mononuclear cells are exposed to viruses ex vivo. Remarkably, infection with vesicular stomatitis virus, vaccinia virus, and a vari...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-09-379479
更新日期:2012-03-29 00:00:00
abstract::IgE and IgE receptors (FcεRI) are well-known inducers of allergy. We recently found in mice that active systemic anaphylaxis depends on IgG and IgG receptors (FcγRIIIA and FcγRIV) expressed by neutrophils, rather than on IgE and FcεRI expressed by mast cells and basophils. In humans, neutrophils, mast cells, basophils...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-07-367334
更新日期:2012-03-15 00:00:00
abstract::In order to determine the prognostic significance of thrombocytosis in idiopathic sideroblastic anemia, the clinical courses of 17 patients were reviewed. Six patients (36%) had thrombocytosis, and none developed acute leukemia. Nine patients (53%) had normal platelet counts, and one developed acute leukemia. Two pati...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI). We have recently found that CD4(+) T cells autoreactive to beta(2)GPI in patients with APS preferentially recognize a cry...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-08-3145
更新日期:2005-02-15 00:00:00
abstract::Because interleukin-10 (IL-10) is a potent differentiation factor of human B cells into mature plasma cells, we investigated its effect on human malignant plasma cells. IL-10 did not induce any differentiation and increase in Ig synthesis in four human IL-6-dependent malignant plasma cell lines. However, it stimulated...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-05-01 00:00:00