Correlation between mononuclear infiltration and changes in VASP phosphorylation patterns after heterotopic cardiac transplantation in the rat
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Correlation between mononuclear infiltration and changes in VASP phosphorylation patterns after heterotopic cardiac transplantation in the rat. / Deuse, T; Lange, V; Schrepfer, S; Eigenthaler, M; Reichart, B; Walter, U; Elert, O.
In: EUR SURG RES, Vol. 35, No. 1, 05.02.2003, p. 6-13.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Correlation between mononuclear infiltration and changes in VASP phosphorylation patterns after heterotopic cardiac transplantation in the rat
AU - Deuse, T
AU - Lange, V
AU - Schrepfer, S
AU - Eigenthaler, M
AU - Reichart, B
AU - Walter, U
AU - Elert, O
N1 - Copyright 2003 S. Karger AG, Basel
PY - 2003/2/5
Y1 - 2003/2/5
N2 - Chronic cardiac transplant vasculopathy still remains the major cause of late graft failure after the 1st postoperative year, with iNOS playing a central role in the progression of this disease. Since VASP, a recently identified microfilament-associated protein in smooth muscle cells, endothelial cells, and platelets, is phosphorylated by cyclic nucleotide dependent protein kinases, changing amounts of NO-producing mononuclear infiltration cells during cardiac rejection are supposed to change platelet VASP phosphorylation patterns. We investigated whether platelet VASP Ser(157) phosphorylation (VASP shift) after coronary passage of rat cardiac allografts correlates with graft infiltration. The Lew-F344 heterotopic rat cardiac transplantation model was used. Native hearts and grafts were harvested 3-150 days after transplantation and were used for Langendorff perfusion. The platelet VASP shift after native heart and graft perfusion was identified. Additional iNOS stimulation and iNOS inhibition were achieved pharmacologically. Immunohistology revealed graft mononuclear infiltration. Platelet VASP Ser(157) and Ser(239) phosphorylation significantly increased after coronary passage of native hearts and grafts (p < 0.01). Though platelet VASP Ser(157) phosphorylation failed to directly express graft infiltration, we showed a significant correlation between changes of platelet VASP shift and extent of grafts' mononuclear infiltration after competitive iNOS inhibition (p < 0.01). The platelet VASP shift is modified during coronary perfusion, and this modification correlates with mononuclear infiltration in the graft. This emphasizes the influence of mononuclear infiltration cells on microfilamental structures of the cytoskeleton in adjacent cells.
AB - Chronic cardiac transplant vasculopathy still remains the major cause of late graft failure after the 1st postoperative year, with iNOS playing a central role in the progression of this disease. Since VASP, a recently identified microfilament-associated protein in smooth muscle cells, endothelial cells, and platelets, is phosphorylated by cyclic nucleotide dependent protein kinases, changing amounts of NO-producing mononuclear infiltration cells during cardiac rejection are supposed to change platelet VASP phosphorylation patterns. We investigated whether platelet VASP Ser(157) phosphorylation (VASP shift) after coronary passage of rat cardiac allografts correlates with graft infiltration. The Lew-F344 heterotopic rat cardiac transplantation model was used. Native hearts and grafts were harvested 3-150 days after transplantation and were used for Langendorff perfusion. The platelet VASP shift after native heart and graft perfusion was identified. Additional iNOS stimulation and iNOS inhibition were achieved pharmacologically. Immunohistology revealed graft mononuclear infiltration. Platelet VASP Ser(157) and Ser(239) phosphorylation significantly increased after coronary passage of native hearts and grafts (p < 0.01). Though platelet VASP Ser(157) phosphorylation failed to directly express graft infiltration, we showed a significant correlation between changes of platelet VASP shift and extent of grafts' mononuclear infiltration after competitive iNOS inhibition (p < 0.01). The platelet VASP shift is modified during coronary perfusion, and this modification correlates with mononuclear infiltration in the graft. This emphasizes the influence of mononuclear infiltration cells on microfilamental structures of the cytoskeleton in adjacent cells.
KW - Animals
KW - Blood Platelets/metabolism
KW - Cell Adhesion Molecules/metabolism
KW - Coronary Circulation
KW - Enzyme Inhibitors/pharmacology
KW - Heart Transplantation
KW - Humans
KW - Immunohistochemistry
KW - Microfilament Proteins
KW - Monocytes/pathology
KW - Myocardium/enzymology
KW - Nitric Oxide Synthase/antagonists & inhibitors
KW - Nitric Oxide Synthase Type II
KW - Nitroarginine/pharmacology
KW - Phosphoproteins/metabolism
KW - Phosphorylation
KW - Rats
KW - Rats, Inbred F344
KW - Rats, Inbred Lew
KW - Transplantation, Heterotopic
U2 - 10.1159/000067036
DO - 10.1159/000067036
M3 - SCORING: Journal article
C2 - 12566781
VL - 35
SP - 6
EP - 13
JO - EUR SURG RES
JF - EUR SURG RES
SN - 0014-312X
IS - 1
ER -