Role of osteopontin in the development of neointimal hyperplasia in vein grafts.
OBJECTIVE
Neointimal hyperplasia and superimposed atherosclerosis are central to late vein graft failure following coronary artery bypass grafting. Recent studies on post-injury arterial vessels have suggested a role of osteopontin (OPN) in the process of vascular remodelling. This study was designed to assess the in vivo performance of OPN following vein grafting.


METHODS
Bilateral saphenous vein-carotid artery interposition grafting was performed in 16 Large White pigs (35-45 kg). All patent vein grafts were removed and fixed at 1, 2, 4 (n = 8 grafts in each group) and 12 weeks (n = 6 grafts) following surgery. Multiple histological sections from each graft were prepared. The expression of OPN in the vein grafts was determined by immunostaining and western blot assay. Proliferating cell nuclear antigen (PCNA) was detected by immunocytochemistry. Vein graft morphology was assessed using computer-aided planimetry.


RESULTS
The expression of OPN remarkably increased in the intima of the vein grafts at the first week postoperatively and then gradually declined from the second postoperative week, although OPN expression remained significantly higher than the baseline level at the end of the 3-month study period. More importantly, the number of PCNA-positive cells and matrix metalloproteinases (MMPs) expression correlated well with the OPN expression.


CONCLUSIONS
Early induction of OPN in vein grafts may contribute to the subsequent increase in MMPs activities as well as vascular smooth muscle cell proliferation. Therefore, OPN could play an important role in the development of neointimal hyperplasia in venous conduits after coronary artery bypass grafting.
Division of Cardiothoracic Surgery, Department of Surgery,  Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong,  China.
Ning
N
Kang
Calvin S H
CS
Ng
Jia
J
Hu
Zhi-Bing
ZB
Qiu
Malcolm J
MJ
Underwood
Jamie Y
JY
Jeremy
Song
S
Wan
D000714:Anastomosis, Surgical / Q000379:methods; D000818:Animals; D002339:Carotid Arteries / Q000601:surgery; D049109:Cell Proliferation; D001026:Coronary Artery Bypass; D006084:Graft Rejection; D006965:Hyperplasia / Q000378:metabolism / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D058426:Neointima / Q000378:metabolism / Q000473:pathology*; D053495:Osteopontin / Q000378:metabolism / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012501:Saphenous Vein / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D034421:Sus scrofa; D017539:Tunica Intima / Q000473:pathology
D018809:Proliferating Cell Nuclear Antigen; D053495:Osteopontin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9