FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2742203396> ?p ?o ?g. }

• W2742203396 endingPage "2081" @default.
• W2742203396 startingPage "2080" @default.
• W2742203396 abstract "In the interesting study by Zhou et al. 1.Zhou J. Kochan J. Yin O. Warren V. Zamora C. Atiee G. Pav J. Orihashi Y. Vashi V. Dishy V. A first‐in‐human study of DS‐1040, an inhibitor of the activated form of thrombin‐activatable fibrinolysis inhibitor, in healthy subjects.J Thromb Haemost. 2017; 15: 961-71Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar of a thrombin‐activatable fibrinolysis inhibitor (TAFI), DS1040, the authors state (p. 962, column 1, paragraph 3) that ‘When plasmin cleaves fibrin … [it] exposes C‐terminal lysine residues [that] can bind both plasminogen and tPA.’ Although this is technically correct, it is functionally misleading, as is also Fig. 1 showing tissue‐type plasminogen activator (t‐PA) binding to lysines. The reason is that the lysine affinity of t‐PA is the same as that of plasminogen 2.Yakovlev S. Makogonenko E. Kurochkina N. Nieuwenhuizen W. Ingham K. Medved L. Conversion of fibrinogen to fibrin: mechanism of exposure of tPA‐ and plasminogen‐binding sites.Biochemistry. 2000; 39: 15730-41Crossref PubMed Scopus (104) Google Scholar. As a consequence, owing to the 1000‐fold molar excess of plasminogen over t‐PA in plasma, these binding sites are essentially saturated by plasminogen, precluding any significant t‐PA binding 3.Medved L. Nieuwenhuizen W. Molecular mechanisms of initiation of fibrinolysis by fibrin.Thromb Haemost. 2003; 89: 409-19Crossref PubMed Scopus (175) Google Scholar. Therefore, in ‘endogenous fibrinolysis’, these sites are not available for ‘propagating fibrinolysis’ by t‐PA, as suggested by the authors (p. 962, column 1, paragraph 3 and Fig. 1). This fact is also important conceptually, because fibrinolysis, as envisioned by the authors, perpetuates the idea that t‐PA alone can be responsible for it under physiologic conditions. Fibrinolytic therapy was also based on this concept. In contrast to lysine‐dependent binding, t‐PA has an exclusive binding site located on the γ‐chain (312–324) of the fibrin D‐domain, which is high‐affinity and lysine‐independent, and is mediated by the t‐PA finger domain 4.Weisel J.W. Nagaswami C. Korsholm B. Petersen L.C. Suenson E. Interactions of plasminogen with polymerized fibrin and its derivatives, monitored with photoaffinity cross‐linker and electron microscopy.J Mol Biol. 1994; 235: 1117-35Crossref PubMed Scopus (65) Google Scholar. The t‐PA affinity for this fibrin site is sufficiently selective and strong that it was possible to purify t‐PA directly from plasma by a single passage over fibrin‐coated celite particles from which t‐PA alone was eluted 5.Husain S.S. Lipinski B. Gurewich V. Rapid purification of high affinity plasminogen activator from human plasma by specific adsorption on fibrin‐celite.Proc Natl Acad Sci USA. 1981; 78: 4265-9Crossref PubMed Scopus (44) Google Scholar. In fibrinolysis, after this high‐affinity site initiates fibrinolysis, plasminogen activation is probably augmented by lysine‐dependent binding, as there is evidence that both of these binding sites are involved in this step 3.Medved L. Nieuwenhuizen W. Molecular mechanisms of initiation of fibrinolysis by fibrin.Thromb Haemost. 2003; 89: 409-19Crossref PubMed Scopus (175) Google Scholar. The new C‐terminal lysine‐binding sites created after the initiation of fibrinolysis, referred to by the authors and shown in Fig. 1, can only be occupied by plasminogen, and cannot ‘propagate tPA fibrinolysis’ under physiologic conditions. The first of these is a triple C‐terminal lysine on the fibrin E‐domain which induces a special conformational change in plasminogen 6.Liu J. Gurewich V. Fragment E‐2 from fibrin substantially enhances pro‐urokinase‐induced glu‐plasminogen activation. A kinetic study using a plasmin‐resistant mutant pro‐urokinase (Ala‐158‐rpro‐UK).Biochemistry. 1992; 31: 6311-17Crossref PubMed Scopus (63) Google Scholar. This enables plasminogen activation by the zymogen form of urokinase plasminogen activator (u‐PA), pro‐u‐PA, owing to a high substrate affinity for this conformation. Plasminogen activation is then accompanied by reciprocal activation of pro‐u‐PA to two‐chain u‐PA (tc‐u‐PA) 7.Petersen L.C. Kinetics of reciprocal pro‐urokinase/plasminogen activation. Stimulation by a template formed by the urokinase receptor bound to poly (D‐lysine).Eur J Biochem. 1997; 245: 316-23Crossref PubMed Scopus (29) Google Scholar, and tc‐u‐PA activates the remaining plasminogen, completing fibrinolysis 8.Gurewich V. Therapeutic fibrinolysis. How efficacy and safety can be improved.J Am Coll Cardiol. 2016; 68: 2099-106Crossref Scopus (15) Google Scholar. Therefore, endogenous fibrinolysis, as envisioned by the authors, cannot function with t‐PA alone but requires both activators. Thus, the DS‐1040 preservation of C‐terminal lysines that TAFI would have removed is more likely to preserve u‐PA‐mediated than t‐PA‐mediated fibrinolysis. Similarly, it has been shown that carboxypeptidase‐B, which has the same substrate specificity as TAFI, inhibits clot lysis by pro‐u‐PA but not that by t‐PA 9.Pannell R. Black J. Gurewich V. The complementary modes of action of tissue plasminogen activator (t‐PA) and pro‐urokinase (pro‐UK) by which their synergistic effect on clot lysis may be explained.J Clin Invest. 1988; 81: 853-9Crossref PubMed Scopus (108) Google Scholar. Both authors contributed to the writing and preparation of this letter to the editor. The authors state that they have no conflict of interest." @default.
• W2742203396 created "2017-08-17" @default.
• W2742203396 creator A5009650479 @default.
• W2742203396 creator A5023321098 @default.
• W2742203396 date "2017-10-01" @default.
• W2742203396 modified "2023-09-30" @default.
• W2742203396 title "A first‐in‐human study of DS‐1040, an inhibitor of the activated form of thrombin‐activatable fibrinolysis inhibitor, in healthy subjects: comment" @default.
• W2742203396 cites W1494479650 @default.
• W2742203396 cites W1893661163 @default.
• W2742203396 cites W2022372977 @default.
• W2742203396 cites W2022944715 @default.
• W2742203396 cites W2033946568 @default.
• W2742203396 cites W2055197581 @default.
• W2742203396 cites W2075518123 @default.
• W2742203396 cites W2548234471 @default.
• W2742203396 cites W2588090681 @default.
• W2742203396 doi "https://doi.org/10.1111/jth.13797" @default.
• W2742203396 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28799246" @default.
• W2742203396 hasPublicationYear "2017" @default.
• W2742203396 type Work @default.
• W2742203396 sameAs 2742203396 @default.
• W2742203396 citedByCount "1" @default.
• W2742203396 countsByYear W27422033962018 @default.
• W2742203396 crossrefType "journal-article" @default.
• W2742203396 hasAuthorship W2742203396A5009650479 @default.
• W2742203396 hasAuthorship W2742203396A5023321098 @default.
• W2742203396 hasBestOaLocation W27422033961 @default.
• W2742203396 hasConcept C126322002 @default.
• W2742203396 hasConcept C153911025 @default.
• W2742203396 hasConcept C181199279 @default.
• W2742203396 hasConcept C185592680 @default.
• W2742203396 hasConcept C203014093 @default.
• W2742203396 hasConcept C2776572282 @default.
• W2742203396 hasConcept C2776825266 @default.
• W2742203396 hasConcept C2777292125 @default.
• W2742203396 hasConcept C2779036427 @default.
• W2742203396 hasConcept C2779672106 @default.
• W2742203396 hasConcept C2779679481 @default.
• W2742203396 hasConcept C2780675426 @default.
• W2742203396 hasConcept C2781071845 @default.
• W2742203396 hasConcept C54173615 @default.
• W2742203396 hasConcept C55493867 @default.
• W2742203396 hasConcept C71924100 @default.
• W2742203396 hasConcept C86803240 @default.
• W2742203396 hasConcept C89560881 @default.
• W2742203396 hasConceptScore W2742203396C126322002 @default.
• W2742203396 hasConceptScore W2742203396C153911025 @default.
• W2742203396 hasConceptScore W2742203396C181199279 @default.
• W2742203396 hasConceptScore W2742203396C185592680 @default.
• W2742203396 hasConceptScore W2742203396C203014093 @default.
• W2742203396 hasConceptScore W2742203396C2776572282 @default.
• W2742203396 hasConceptScore W2742203396C2776825266 @default.
• W2742203396 hasConceptScore W2742203396C2777292125 @default.
• W2742203396 hasConceptScore W2742203396C2779036427 @default.
• W2742203396 hasConceptScore W2742203396C2779672106 @default.
• W2742203396 hasConceptScore W2742203396C2779679481 @default.
• W2742203396 hasConceptScore W2742203396C2780675426 @default.
• W2742203396 hasConceptScore W2742203396C2781071845 @default.
• W2742203396 hasConceptScore W2742203396C54173615 @default.
• W2742203396 hasConceptScore W2742203396C55493867 @default.
• W2742203396 hasConceptScore W2742203396C71924100 @default.
• W2742203396 hasConceptScore W2742203396C86803240 @default.
• W2742203396 hasConceptScore W2742203396C89560881 @default.
• W2742203396 hasIssue "10" @default.
• W2742203396 hasLocation W27422033961 @default.
• W2742203396 hasLocation W27422033962 @default.
• W2742203396 hasOpenAccess W2742203396 @default.
• W2742203396 hasPrimaryLocation W27422033961 @default.
• W2742203396 hasRelatedWork W1990987600 @default.
• W2742203396 hasRelatedWork W2002364719 @default.
• W2742203396 hasRelatedWork W2035296495 @default.
• W2742203396 hasRelatedWork W2037064786 @default.
• W2742203396 hasRelatedWork W2042876710 @default.
• W2742203396 hasRelatedWork W2466223857 @default.
• W2742203396 hasRelatedWork W2742203396 @default.
• W2742203396 hasRelatedWork W2883103643 @default.
• W2742203396 hasRelatedWork W2904535710 @default.
• W2742203396 hasRelatedWork W4304481013 @default.
• W2742203396 hasVolume "15" @default.
• W2742203396 isParatext "false" @default.
• W2742203396 isRetracted "false" @default.
• W2742203396 magId "2742203396" @default.
• W2742203396 workType "article" @default.