Plasminogen is a critical regulator of cutaneous wound healing.

Abstract:

:Wound healing is a complicated biological process that consist of partially overlapping inflammatory, proliferation and tissue remodelling phases. A successful wound healing depends on a proper activation and subsequent termination of the inflammatory phase. The failure to terminate the inflammation halts the completion of wound healing and is a known reason for formation of chronic wounds. Previous studies have shown that wound closure is delayed in plasminogen-deficient mice, and a role for plasminogen in dissection of extracellular matrix was suggested. However, our finding that plasminogen is transported to the wound by inflammatory cells early during the healing process, where it potentiates inflammation, indicates that plasminogen may also have other roles in the wound healing process. Here we report that plasminogen-deficient mice have extensive fibrin and neutrophil depositions in the wounded area long after re-epithelialisation, indicating inefficient debridement and chronic inflammation. Delayed formation of granulation tissue suggests that fibroblast function is impaired in the absence of plasminogen. Therefore, in addition to its role in the activation of inflammation, plasminogen is also crucial for subsequent steps, including resolution of inflammation and activation of the proliferation phase. Importantly, supplementation of plasminogen-deficient mice with human plasminogen leads to a restored healing process that is comparable to that in wild-type mice. Besides of being an activator of the inflammatory phase during wound healing, plasminogen is also required for the subsequent termination of inflammation. Based on these results, we propose that plasminogen may be an important future therapeutic agent for wound treatment.

journal_name

Thromb Haemost

authors

Sulniute R,Shen Y,Guo YZ,Fallah M,Ahlskog N,Ny L,Rakhimova O,Broden J,Boija H,Moghaddam A,Li J,Wilczynska M,Ny T

doi

10.1160/TH15-08-0653

subject

Has Abstract

pub_date

2016-05-02 00:00:00

pages

1001-9

issue

5

eissn

0340-6245

issn

2567-689X

pii

15-08-0653

journal_volume

115

pub_type

杂志文章
  • Endothelial cells produce a lipoxygenase derived chemo-repellent which influences platelet/endothelial cell interactions--effect of aspirin and salicylate.

    abstract::We performed experiments to determine whether endothelial cells synthesize phospholipid metabolites via the lipoxygenase pathway and whether these metabolites influence platelet/vessel wall interactions. Monolayers of cultured human endothelial cells were incubated with 14C-arachidonic acid and their cyclo-oxygenase a...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Buchanan MR,Butt RW,Magas Z,van Ryn J,Hirsh J,Nazir DJ

    更新日期:1985-06-24 00:00:00

  • Ouabain enhances basal and stimulus-induced cytoplasmic calcium concentrations in platelets.

    abstract::Incubation of platelet-rich plasma (PRP) with ouabain, an inhibitor of sodium/potassium ATPase (Na+/K+ ATPase), induced a significant rise in basal platelet intracellular calcium concentration [( Ca2+]i) when measured using fura 2. Ouabain induced an enhanced aggregation response to low doses of collagen in both PRP a...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Lees AD,Wilson J,Orchard CH,Orchard MA

    更新日期:1989-11-24 00:00:00

  • Effect of tissue factor pathway inhibitor (TFPI) in the HEPTEST assay and in an amidolytic anti factor Xa assay for LMW heparin.

    abstract::Both the HEPTEST and amidolytic anti factor Xa assays are currently being used for heparin activity detection in plasma from patients receiving standard heparin or low molecular weight heparin (LMWH). In this study we have investigated the influence of recombinant and endogenous Tissue Factor Pathway Inhibitor (TFPI) ...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Kristensen HI,Ostergaard PB,Nordfang O,Abildgaard U,Lindahl AK

    更新日期:1992-09-07 00:00:00

  • Fibrinopeptide A release is necessary for effective B:b interactions in polymerisation of variant fibrinogens with impaired A:a interactions.

    abstract::Fibrin polymerisation is mediated by interactions between knobs 'A' and 'B' exposed by thrombin cleavage, and holes 'a' and 'b'. We demonstrated markedly delayed thrombin-catalysed fibrin polymerisation, through B:b interactions alone, of recombinant γD364H -fibrinogen with impaired hole 'a'. To determine whether reco...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:10.1160/TH12-09-0684

    authors: Soya K,Terasawa F,Okumura N

    更新日期:2013-02-01 00:00:00

  • Enhanced TNF alpha and oxidative stress in patients with heart failure: effect of TNF alpha on platelet O2- production.

    abstract::Experimental studies have suggested that TNF alpha, a pro-inflammatory cytokine, may contribute to the deterioration of cardiovascular function through various mechanisms, including the generation of reactive oxygen species. It has not yet been demonstrated whether TNF alpha has prooxidant activity in patients with he...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:10.1160/TH03-02-0105

    authors: De Biase L,Pignatelli P,Lenti L,Tocci G,Piccioni F,Riondino S,Pulcinelli FM,Rubattu S,Volpe M,Violi F

    更新日期:2003-08-01 00:00:00

  • Plasminogen activator and plasminogen activator inhibitor associated with granulomatous inflammation: a study with murine leprosy.

    abstract::Plasminogen activator that is associated with the development of hypersensitivity granulomas (gPA) was partially purified from a saline soluble fraction of murine lepromas elicited in "resistant" mice, C57BL/6N. The gPA was shown to consist of two subspecies (23,000 and 48,000 in molecular weight) with essentially ide...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Izaki S,Hibino T,Isozaki Y,Hsu PS,Izaki M,Matsuo O

    更新日期:1984-12-29 00:00:00

  • A randomised trial on platelet function-guided de-escalation of antiplatelet treatment in ACS patients undergoing PCI. Rationale and design of the Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment for Acute Coronary Syndromes

    abstract::Outcomes of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) have been significantly improved with the use of potent P2Y12 receptor inhibitors like prasugrel. While most of the ischaemic risk reduction for prasugrel versus clopidogrel was demonstrated in the early treatment pe...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1160/TH16-07-0557

    authors: Sibbing D,Aradi D,Jacobshagen C,Gross L,Trenk D,Geisler T,Orban M,Gori T,Hadamitzky M,Merkely B,Kiss RG,Komócsi A,Dézsi CA,Thalmeier A,Löw A,Holdt L,Teupser D,Ince H,Felix SB,Parma R,Malek L,Horstkotte J,Bayla

    更新日期:2017-01-05 00:00:00

  • Multistate Models: Accurate and Dynamic Methods to Improve Predictions of Thrombotic Risk in Patients with Cancer.

    abstract::Research into cancer-associated thrombosis (CAT) entails managing dynamic data that pose an analytical challenge. Thus, methods that assume proportional hazards to investigate prognosis entail a risk of misinterpreting or overlooking key traits or time-varying effects. We examined the AGAMENON registry, which collects...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章,多中心研究

    doi:10.1055/s-0039-1694012

    authors: Carmona-Bayonas A,Jimenez-Fonseca P,Garrido M,Custodio A,Hernandez R,Lacalle A,Cano JM,Aguado G,Martínez de Castro E,Alvarez Manceñido F,Macias I,Visa L,Martín Richard M,Mangas M,Sánchez Cánovas M,Longo F,Iglesias Rey L,

    更新日期:2019-11-01 00:00:00

  • CX3CR1/CX3CL1 Axis Mediates Platelet-Leukocyte Adhesion to Arterial Endothelium in Younger Patients with a History of Idiopathic Deep Vein Thrombosis.

    abstract::Mechanisms linking deep vein thrombosis (DVT) and subclinical atherosclerosis and risk of cardiovascular events are poorly understood. The aim of this study was to investigate the potential impact of CX3CR1/CX3CL1 axis in DVT-associated endothelial dysfunction. The study included 22 patients (age: 37.5 ± 8.2 years) wi...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:10.1055/s-0038-1629897

    authors: Furio E,García-Fuster MJ,Redon J,Marques P,Ortega R,Sanz MJ,Piqueras L

    更新日期:2018-03-01 00:00:00

  • Identifying Sepsis Populations Benefitting from Anticoagulant Therapy: A Prospective Cohort Study Incorporating a Restricted Cubic Spline Regression Model.

    abstract:BACKGROUND: Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsis patients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章,多中心研究

    doi:10.1055/s-0039-1693740

    authors: Yamakawa K,Gando S,Ogura H,Umemura Y,Kabata D,Shintani A,Shiraishi A,Saitoh D,Fujishima S,Mayumi T,Kushimoto S,Abe T,Shiino Y,Nakada TA,Tarui T,Hifumi T,Otomo Y,Okamoto K,Kotani J,Sakamoto Y,Sasaki J,Shiraishi S

    更新日期:2019-11-01 00:00:00

  • Ex vivo effects of low-dose rivaroxaban on specific coagulation assays and coagulation factor activities in patients under real life conditions.

    abstract::Global coagulation assays display variable effects at different concentrations of rivaroxaban. The aim of this study is to quantify the ex vivo effects of low-dose rivaroxaban on thrombophilia screening assays and coagulation factor activities based on the administration time, and to show how to mask possible inter...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:10.1160/TH12-04-0228

    authors: Mani H,Hesse C,Stratmann G,Lindhoff-Last E

    更新日期:2013-01-01 00:00:00

  • Binding of tissue plasminogen activator to vascular grafts.

    abstract::Tissue plasminogen activator labeled with radioactive iodine (125I-tPA) was immobilized on vascular prostheses chemically modified with a thin coating of water-insoluble surfactant, tridodecylmethylammonium chloride (TDMAC). Surfactant-treated Dacron, polytetrafluoroethylene (PTFE), silastic, polyethylene and polyuret...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Harvey RA,Kim HC,Pincus J,Trooskin SZ,Wilcox JN,Greco RS

    更新日期:1989-02-28 00:00:00

  • Low density lipoprotein receptor-related protein: regulation of the plasma membrane proteome.

    abstract::Proteins in the plasma membrane anchor the cell within its microenvironment and sense changes occurring outside the cell. The anchoring interactions are cell type-specific and may involve adjacent cells or extracellular matrix proteins (ECMPs). In development, wound healing, and in various forms of pathology, includin...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章,评审

    doi:10.1160/TH04-01-0023

    authors: Gonias SL,Wu L,Salicioni AM

    更新日期:2004-06-01 00:00:00

  • Thrombin production, inactivation and expression during open heart surgery measured by assays for activation fragments including a new ELISA for prothrombin fragment F1 + 2.

    abstract::Activation of coagulation was studied during the peri-operative period in patients undergoing cardiopulmonary bypass (CPB) surgery using activation markers which have recently become available: prothrombin fragment F1 + 2 (F1 + 2), which is a measure of total thrombin generation, and thrombin-antithrombin complex, whi...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Boisclair MD,Lane DA,Philippou H,Sheikh S,Hunt B

    更新日期:1993-08-02 00:00:00

  • Impaired prothrombin consumption in Bernard-Soulier syndrome is corrected in vitro by human factor VIII.

    abstract::The Bernard-Soulier syndrome (BSS) is characterized by thrombocytopenia with giant platelets, a prolonged bleeding time with defective platelet adhesion to the subendothelium related to a defect in platelet membrane glycoprotein Ib (GPIb) and a decreased prothrombin consumption. The mechanism of the latter abnormality...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Bellucci S,Girma JP,Lozano M,Meyer D,Caen JP

    更新日期:1997-02-01 00:00:00

  • High molecular weight forms of antithrombin III complexes in blood.

    abstract::A double antibody competition radioimmunoassay was developed that allowed to detect specifically as little as 15 ng antithrombin III (AT III) per ml of the assayed material. In normal plasma examined by this assay, AT III concentration averaged 199 +/- 21 micrograms/ml. Complexes of AT III with thrombin or factor Xa c...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Marciniak E,Gora-Maslak G

    更新日期:1983-02-28 00:00:00

  • Thrombin generation in rheumatoid arthritis: dependence on plasma factor composition.

    abstract::Growing evidence indicates that rheumatoid arthritis (RA) is associated with an increased risk for thromboembolic cardiovascular events. We investigated thrombin generation profiles in RA patients and their dependence on plasma factor/inhibitor composition. Plasma factor (F) compositions (II, V, VII, VIII, IX, X), ant...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:10.1160/TH10-02-0091

    authors: Undas A,Gissel M,Kwasny-Krochin B,Gluszko P,Mann KG,Brummel-Ziedins KE

    更新日期:2010-08-01 00:00:00

  • Mouse protein Z-dependent protease inhibitor cDNA.

    abstract::Protein Z-dependent protease inhibitor (ZPI) is plasma proteinase inhibitor in the serpin superfamily that produces rapid inhibition of factor Xa in the presence of phospholipids, Ca++ and protein Z (PZ). Mouse ZPI cDNA was isolated and cloned from mouse liver RNA using RT-PCR. The cDNA contains 100 nucleotides 5' of ...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Zhang J,Broze GJ Jr

    更新日期:2001-05-01 00:00:00

  • Platelet Glycoprotein VI Haplotypes and the Presentation of Paediatric Sepsis.

    abstract::Sepsis triggers a complex series of pathophysiologic events involving inflammatory responses and coagulation abnormalities. While circulating blood platelets are well-characterized for their contributions to coagulation, increasingly platelet-dependent effects on inflammation are being recognized. Here, we focus on th...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:10.1055/s-0038-1676794

    authors: Asfari A,Dent JA,Corken A,Herington D,Kaliki V,Sra N,Hefley G,Pasala S,Prodhan P,Ware J

    更新日期:2019-03-01 00:00:00

  • Beta-TG and plasma catecholamines levels after sympathetic stimuli in hypertensives and patients with peripheral vascular disease.

    abstract::The influence of the sympathetic nervous system on platelet functions in vivo is still controversial. The aims of our study were to compare the response to various sympathetic stimuli in normal subjects and in patients with essential hypertension (HT) or peripheral vascular disease (PVD) and to evaluate any correlatio...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Catalano M,Russo U,Belletti S,Colombo F,Belloni A,del Rosso G,Lombardi F,Libretti A

    更新日期:1990-06-28 00:00:00

  • Prostaglandin-endoperoxide synthase-2 deletion affects the natural trafficking of Annexin A2 in monocytes and favours venous thrombosis in mice.

    abstract::Deep-vein thrombosis (DVT) is a common condition that often leads to pulmonary thromboembolism (VTE) and death. The role of prostaglandin-endoperoxide synthase (PTGS)2 in arterial thrombosis has been well established, whereas its impact in venous thrombosis remains unclear. Here, we showed that PTGS2 deletion predispo...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:10.1160/TH16-12-0968

    authors: Amadio P,Tarantino E,Sandrini L,Tremoli E,Barbieri SS

    更新日期:2017-07-26 00:00:00

  • Neuroserpin: a selective inhibitor of tissue-type plasminogen activator in the central nervous system.

    abstract::Neuroserpin is a member of the serine proteinase inhibitor (serpin) gene family that reacts preferentially with tissue-type plasminogen activator (tPA) and is primarily localized to neurons in regions of the brain where tPA is also found. Outside of the central nervous system (CNS) tPA is predominantly found in the bl...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章,评审

    doi:10.1160/TH03-12-0766

    authors: Yepes M,Lawrence DA

    更新日期:2004-03-01 00:00:00

  • Increased plasma thrombin-antithrombin III complex levels in non-insulin dependent diabetic patients with albuminuria are reduced by ethyl icosapentatenoate.

    abstract::Hypercoagulability may increase the risk of cardiovascular disease (CVD) in diabetic patients with albuminuria. Plasma thrombin-anti-thrombin III complex (TAT) levels, representing a functional state of clotting system, were studied in one hundred and fifteen non-insulin-dependent diabetic (NIDDM) patients. The patien...

    journal_title:Thrombosis and haemostasis

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Shimizu H,Ohtani K,Tanaka Y,Fukatsu A,Uehara Y,Sato N,Mori M

    更新日期:1995-11-01 00:00:00

  • Thrombin generation, a function test of the haemostatic-thrombotic system.

    abstract::By the use of a fluorogenic thrombin substrate and continuous calibration of each individual sample, it is now possible to obtain a thrombin generation (TG) curve (or thrombogram) in plasma, with or without platelets, in an easy routine procedure at high throughput and with an acceptable experimental error (<5%). Evid...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章,评审

    doi:

    authors: Hemker HC,Al Dieri R,De Smedt E,Béguin S

    更新日期:2006-11-01 00:00:00

  • Blood coagulation factor X deficiency causes partial embryonic lethality and fatal neonatal bleeding in mice.

    abstract::Mice with a total deficiency in blood coagulation Factor X (FX) were generated by targeted replacement of an 18-kb fragment of the FX gene, comprising all exons encoding the mature FX protein, with a neo(r) cassette. The genotype distribution among the offspring from heterozygous breeding pairs suggested that FX defic...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Dewerchin M,Liang Z,Moons L,Carmeliet P,Castellino FJ,Collen D,Rosen ED

    更新日期:2000-02-01 00:00:00

  • Vitamin K-dependent protein production in transgenic animals.

    abstract::Vitamin K-dependent proteins are currently purified from pooled human plasma or produced in mammalian cell culture systems by recombinant DNA technology. Transgenic animals may provide an additional expression system for the production of these therapeutic proteins. Mice have been used to test hybrid genes which direc...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章,评审

    doi:

    authors: Luboń H,Paleyanda RK

    更新日期:1997-07-01 00:00:00

  • Proteasome Inhibition with Bortezomib Induces Apoptosis of Long-Lived Plasma Cells in Steroid-Resistant or Relapsed Immune Thrombocytopaenia.

    abstract::Primary immune thrombocytopaenia (ITP) is the most common haemorrhagic disease. Although most patients respond initially to mainstream therapies, such as corticosteroids, immunosuppressants or rituximab, a large proportion of patients fail to respond or relapse. These treatments only affect B lymphocytes or short-live...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:10.1055/s-0038-1669921

    authors: Li G,Wang S,Li N,Liu Y,Feng Q,Zuo X,Li X,Hou Y,Shao L,Ma C,Gao C,Hou M,Peng J

    更新日期:2018-10-01 00:00:00

  • Overcoming Heparin-Associated RT-qPCR Inhibition and Normalization Issues for microRNA Quantification in Patients with Acute Myocardial Infarction.

    abstract:BACKGROUND: Cardiac-enriched micro ribonucleic acids (miRNAs) are released into the circulation following ST-elevation myocardial infarction (STEMI). Lack of standardized approaches for reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) data normalization and presence of RT-qPCR inhibitors...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:10.1055/s-0038-1660437

    authors: Coelho-Lima J,Mohammed A,Cormack S,Jones S,Das R,Egred M,Panahi P,Ali S,Spyridopoulos I

    更新日期:2018-07-01 00:00:00

  • 4G/5G promoter PAI-1 gene polymorphism is associated with plasmatic PAI-1 activity in Italians: a model of gene-environment interaction.

    abstract::The PAI-1 gene promoter 4G/5G polymorphism was found to be associated with plasma PAI-1 activity in Northern and Central Europe populations, but no data are available on the association between this polymorphism and PAI-1 levels in Southern Europe countries (such as Italy) where the incidence of ischemic disorders is ...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Burzotta F,Di Castelnuovo A,Amore C,D'Orazio A,Di Bitondo R,Donati MB,Iacoviello L

    更新日期:1998-02-01 00:00:00

  • In vitro and in vivo effects of adrenaline and phentolamine on platelet function.

    abstract::In vitro and in vivo effects of adrenaline (ADR) on platelet aggregation, on platelet factor 3 (PF3) availability and on platelet factor 4 (PF4) release were studied in man. Inhibitory action of an alpha-blocker, phentolamine (PHEN) was investigated in the same conditions. The threshold concentration (TC) of ADR induc...

    journal_title:Thrombosis and haemostasis

    pub_type: 杂志文章

    doi:

    authors: Ponari O,Civardi E,Megha A,Pini M,Poti' R,Dettori AG

    更新日期:1978-10-31 00:00:00