TY  - JOUR
A1  - Köhler, David
A1  - Birk, Philipp
A1  - König, Klemens
A1  - Straub, Andreas
A1  - Eldh, Therese
A1  - Morote-Garcia, Julio C.
A1  - Rosenberger, Peter
T1  - Phosphorylation of Vasodilator-Stimulated Phosphoprotein (VASP) dampens hepatic ischemia-reperfusion injury
T2  - PLoS One
N2  - 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 Ser153 through Prostaglandin E1 or on Ser235 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.
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/23720
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-237200
SN  - 1932-6203
VL  - 6
IS  - 12: e29494
SP  - 1
EP  - 9
PB  - PLoS
CY  - Lawrence, Kan.
ER  -