Arterialization of a vein graft promotes cell cycle progression through Akt and p38 mitogen-activated protein kinase pathways: impact of the preparation procedure.
BACKGROUND
Vein arterialization following bypass surgery often leads to graft occlusion, but the underlying cellular mechanisms have been poorly studied.


OBJECTIVE
Cell cycle progression and the activation of proliferation signalling were compared in arterialized grafts prepared either according to the conventional procedure or using pharmacological relaxation with the native vein.


METHODS
Using the porcine carotid-jugular bilateral interposition graft model on one side, a segment of porcine jugular vein was prepared for grafting using the conventional procedure, with pressure distention at 300 mmHg; the segment grafted on the other side was treated with a combination of pharmacological vasodilators. Both veins were grafted into the carotid artery for two weeks.


RESULTS
On the immunolabelling of proliferation cell nuclear antigen, a greater number of proliferating cells was found in the conventionally prepared grafts compared with pharmacologically prepared grafts. Cyclin D1 expression and phosphorylation of retinoblastoma increased after implantation, coinciding with nuclear accumulation of beta-catenin, activation of the Akt and mitogen-activated protein kinase cascades, and upregulated phosphatase and tensin homologue phosphorylation. Replacement of distention with pharmacological relaxation reduced the increase in cyclin D1 expression, phosphorylation of retinoblastoma, Akt-Thr(308), glycogen synthase kinase 3 beta and p38, but not extracellular signal-regulated kinases. This technique preserved the active phosphatase and tensin homologue, as well as the expression of cyclin-dependent kinase inhibitor p21(Cip1), while elevating the expression of p27(Kip1).


CONCLUSIONS
It was concluded that two-week arterial implantation stimulates proliferation signalling and promotes the cell cycle in vein grafts. Replacement of the conventional preparation procedures with pharmacological vasorelaxation restricts the activation of proliferation and cell cycle progression, and can be beneficial for improving vein graft patency.
James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Vancouver, Canada. achung@mrl.ubc.ca
Ada W Y
AW
Chung
Jerry
J
Wong
Honglin
H
Luo
York N
YN
Hsiang
Cornelis
C
van Breemen
Elena B
EB
Okon
D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D049109:Cell Proliferation; D003327:Coronary Disease / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007601:Jugular Veins / Q000201:enzymology / Q000473:pathology* / Q000637:transplantation; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000473:pathology; D009389:Neovascularization, Pathologic; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D009927:Tissue and Organ Procurement / Q000379:methods*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
D012313:RNA; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases