Division of Cardiothoracic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Eur J Cardiothorac Surg. 2012 Jun;41(6):1384-9. doi: 10.1093/ejcts/ezr200. Epub 2011 Dec 26.
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.
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.
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.
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.
在冠状动脉旁路移植术后，吻合口内膜增生和叠加的动脉粥样硬化是静脉移植物晚期失败的核心。最近对损伤后动脉血管的研究表明，骨桥蛋白（OPN）在血管重塑过程中起作用。本研究旨在评估 OPN 在静脉移植物后的体内表现。
在 16 头大白猪（35-45kg）中进行双侧大隐静脉-颈动脉间置移植术。所有通畅的静脉移植物在手术后 1、2、4（每组 n = 8 个移植物）和 12 周（n = 6 个移植物）时取出并固定。从每个移植物制备多个组织学切片。通过免疫染色和 Western blot 检测 OPN 在静脉移植物中的表达。通过免疫细胞化学检测增殖细胞核抗原（PCNA）。使用计算机辅助面积测定法评估静脉移植物的形态。
OPN 在术后第一周静脉移植物内膜中的表达显著增加，然后从术后第二周开始逐渐下降，但在 3 个月研究结束时，OPN 的表达仍明显高于基线水平。更重要的是，PCNA 阳性细胞的数量和基质金属蛋白酶（MMPs）的表达与 OPN 的表达密切相关。
早期在静脉移植物中诱导 OPN 可能导致随后 MMPs 活性和血管平滑肌细胞增殖的增加。因此，OPN 可能在冠状动脉旁路移植术后静脉导管中新生内膜增生的发展中起重要作用。
