Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) dampens hepatic ischemia-reperfusion injury.
Recent work has demonstrated that the formation of platelet neutrophil complexes (PNCs) affects inflammatory tissue injury. Vasodilator-stimulated phosphoprotein (VASP) is crucially involved into the control of PNC formation and myocardial reperfusion injury. Given the clinical importance of hepatic...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3245274?pdf=render |
| _version_ | 1819089714591825920 |
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| author | David Köhler Philipp Birk Klemens König Andreas Straub Therese Eldh Julio C Morote-Garcia Peter Rosenberger |
| author_facet | David Köhler Philipp Birk Klemens König Andreas Straub Therese Eldh Julio C Morote-Garcia Peter Rosenberger |
| author_sort | David Köhler |
| collection | DOAJ |
| description | Recent work has demonstrated that the formation of platelet neutrophil complexes (PNCs) affects inflammatory tissue injury. Vasodilator-stimulated phosphoprotein (VASP) is crucially involved into the control of PNC formation and myocardial reperfusion injury. Given the clinical importance of hepatic IR injury we pursued the role of VASP during hepatic ischemia followed by reperfusion. We report here that VASP(-/-) animals demonstrate reduced hepatic IR injury compared to wildtype (WT) controls. This correlated with serum levels of lactate dehydrogenase (LDH), aspartate (AST) and alanine (ALT) aminotransferase and the presence of PNCs within ischemic hepatic tissue and could be confirmed using repression of VASP through siRNA. In studies employing bone marrow chimeric mice we identified hematopoietic VASP to be of crucial importance for the extent of hepatic injury. Phosphorylation of VASP on Ser(153) through Prostaglandin E1 or on Ser(235) through atrial natriuretic peptide resulted in a significant reduction of hepatic IR injury. This was associated with a reduced presence of PNCs in ischemic hepatic tissue. Taken together, these studies identified VASP and VASP phosphorylation as crucial target for future hepatoprotective strategies. |
| first_indexed | 2024-12-21T22:12:20Z |
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| id | doaj.art-e8872523967744e693074c7948a39473 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T22:12:20Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e8872523967744e693074c7948a394732022-12-21T18:48:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01612e2949410.1371/journal.pone.0029494Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) dampens hepatic ischemia-reperfusion injury.David KöhlerPhilipp BirkKlemens KönigAndreas StraubTherese EldhJulio C Morote-GarciaPeter RosenbergerRecent work has demonstrated that the formation of platelet neutrophil complexes (PNCs) affects inflammatory tissue injury. Vasodilator-stimulated phosphoprotein (VASP) is crucially involved into the control of PNC formation and myocardial reperfusion injury. Given the clinical importance of hepatic IR injury we pursued the role of VASP during hepatic ischemia followed by reperfusion. We report here that VASP(-/-) animals demonstrate reduced hepatic IR injury compared to wildtype (WT) controls. This correlated with serum levels of lactate dehydrogenase (LDH), aspartate (AST) and alanine (ALT) aminotransferase and the presence of PNCs within ischemic hepatic tissue and could be confirmed using repression of VASP through siRNA. In studies employing bone marrow chimeric mice we identified hematopoietic VASP to be of crucial importance for the extent of hepatic injury. Phosphorylation of VASP on Ser(153) through Prostaglandin E1 or on Ser(235) through atrial natriuretic peptide resulted in a significant reduction of hepatic IR injury. This was associated with a reduced presence of PNCs in ischemic hepatic tissue. Taken together, these studies identified VASP and VASP phosphorylation as crucial target for future hepatoprotective strategies.http://europepmc.org/articles/PMC3245274?pdf=render |
| spellingShingle | David Köhler Philipp Birk Klemens König Andreas Straub Therese Eldh Julio C Morote-Garcia Peter Rosenberger Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) dampens hepatic ischemia-reperfusion injury. PLoS ONE |
| title | Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) dampens hepatic ischemia-reperfusion injury. |
| title_full | Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) dampens hepatic ischemia-reperfusion injury. |
| title_fullStr | Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) dampens hepatic ischemia-reperfusion injury. |
| title_full_unstemmed | Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) dampens hepatic ischemia-reperfusion injury. |
| title_short | Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) dampens hepatic ischemia-reperfusion injury. |
| title_sort | phosphorylation of vasodilator stimulated phosphoprotein vasp dampens hepatic ischemia reperfusion injury |
| url | http://europepmc.org/articles/PMC3245274?pdf=render |
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