Correlation between mononuclear infiltration and changes in VASP phosphorylation patterns after heterotopic cardiac transplantation in the rat

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 -