Evidence map›Paper›PMID 27197780›Full record

ArticleJournal of cellular and molecular medicine2016

A specific plasminogen activator inhibitor-1 antagonist derived from inactivated urokinase.

Lihu Gong, Valerie Proulle, Chao Fang, Zebin Hong, Zhonghui Lin, Min Liu, Guangpu Xue, Cai Yuan, Lin Lin, Barbara Furie and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cellular and molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Exploring the multifaceted role of obesity in breast cancer progression.Frontiers in cell and developmental biology · 2024
    Review
  3. Review
  4. Endogenous fibrinolysis inhibitors in acute coronary syndrome.American heart journal plus : cardiology research and practice · 2021
    Review
  5. Review
  6. The Importance of Breast Adipose Tissue in Breast Cancer.International journal of molecular sciences · 2020
    Review
  7. Therapeutics targeting the fibrinolytic system.Experimental & molecular medicine · 2020
    Review
  8. Article
  9. Targeting plasminogen activator inhibitor-1 in tetracycline-induced pleural injury in rabbits.American journal of physiology. Lung cellular and molecular physiology · 2018
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 3 countries.

Lihu GongState Key Laboratory of Structural Chemistry and Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, China.
Valerie ProulleDivision of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Chao FangDivision of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Zebin HongState Key Laboratory of Structural Chemistry and Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, China.
Zhonghui LinState Key Laboratory of Structural Chemistry and Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, China.
Min LiuState Key Laboratory of Structural Chemistry and Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, China.
Guangpu XueState Key Laboratory of Structural Chemistry and Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, China.
Cai YuanState Key Laboratory of Structural Chemistry and Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, China.
Lin LinDivision of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Barbara FurieDivision of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Robert FlaumenhaftDivision of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Peter AndreasenDepartment of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
Bruce FurieDivision of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Mingdong HuangState Key Laboratory of Structural Chemistry and Danish-Chinese Centre for Proteases and Cancer, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, China. mhuang@fjirsm.ac.cn.
Beth Israel Deaconess Medical Center · USFujian Institute of Research on the Structure of Matter · CNUniversity of Chinese Academy of Sciences · CNAarhus University · DKChinese Academy of Sciences · CN

Funding

Thrombus Formation In VivoP01HL087203 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FURIE, BRUCE · 2008 to 2012
$8.8M
Cancer, venous thromboembolic disease and tissue factor-bearing microparticlesR01HL095084 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FURIE, BRUCE · 2008 to 2012
$2.1M
NHLBI NIH HHS P01 HL087203NHLBI NIH HHS R01 HL095084
6 · The paper itself

Abstract

Fibrinolysis is a process responsible for the dissolution of formed thrombi to re-establish blood flow after thrombus formation. Plasminogen activator inhibitor-1 (PAI-1) inhibits urokinase-type and tissue-type plasminogen activator (uPA and tPA) and is the major negative regulator of fibrinolysis. Inhibition of PAI-1 activity prevents thrombosis and accelerates fibrinolysis. However, a specific antagonist of PAI-1 is currently unavailable for therapeutic use. We screened a panel of uPA variants with mutations at and near the active site to maximize their binding to PAI-1 and identified a potent PAI-1 antagonist, PAItrap. PAItrap is the serine protease domain of urokinase containing active-site mutation (S195A) and four additional mutations (G37bR-R217L-C122A-N145Q). PAItrap inhibits human recombinant PAI-1 with high potency (Kd = 0.15 nM) and high specificity. In vitro using human plasma, PAItrap showed significant thrombolytic activity by inhibiting endogenous PAI-1. In addition, PAItrap inhibits both human and murine PAI-1, allowing the evaluation in murine models. In vivo, using a laser-induced thrombosis mouse model in which thrombus formation and fibrinolysis are monitored by intravital microscopy, PAItrap reduced fibrin generation and inhibited platelet accumulation following vascular injury. Therefore, this work demonstrates the feasibility to generate PAI-1 inhibitors using inactivated urokinase.

Indexed as

Amino Acid SequenceAnimalsCatalytic DomainCrystallography, X-RayDisease Models, AnimalFibrinolysisHumansInhibitory Concentration 50KineticsMice, Inbred C57BLModels, MolecularMutant ProteinsPeptide FragmentsPlasminogen Activator Inhibitor 1Protein BindingThrombosisMutant ProteinsPAItrap peptidePeptide FragmentsPlasminogen Activator Inhibitor 1Urokinase-Type Plasminogen Activatorantithrombotic agentfibrinolysisPAI-1protein structureurokinase variants

Identifiers

PMID27197780
PMCPMC4876229
OpenAlexW2406606844

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.