Bobryshev Y V, Farnsworth A E, Lord R S
Surgical Professorial Unit, St. Vincent's Hospital, University of New South Wales, NSW 2010, Darlinghurst, Australia.
Cardiovasc Surg. 2001 Oct;9(5):492-8. doi: 10.1016/s0967-2109(01)00040-0.
Neovascularisation is a prominent feature of long-term aortocoronary saphenous vein bypass grafts but mechanisms involved in the formation of neovessels have not been previously studied. Vascular Endothelial Growth Factor (VEGF) is an important angiogenic factor that induces migration and proliferation of endothelial cells, enhances permeability and modulates thrombogenecity. This study investigated the expression of VEGF in aortocoronary saphenous vein bypass grafts. Aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of >75% were explanted from 14 patients at redo coronary artery bypass grafting. The grafts demonstrated two distinct forms of graft occlusion: four out of the 14 graft occlusions (29%) resulted from severe hyperplastic transformation of the intima complicated by thrombi attached to the degenerating liminal endothelium; the remaining graft occlusions (71%) were due to the development of atherosclerotic lesions associated with mural thrombosis. Hiperplastically altered intimal segments were practically free of neovascularisation while atherosclerotic-like lesions contained neovessels irregularly distributed throughout. Intimal neovessels were located exclusively in microzones enriched with VEGF-expressing cells and, furthermore, neovascular endothelial cells themselves also displayed VEGF immunopositivity. Double-immunostaining revealed that in areas of neovascularisation, the vast majority macrophages (CD68+) expressed VEGF. Some CD68+ foam cells that surrounded branches of neovascularisation were also VEGF-positive. These findings suggest that VEGF expressed by neovascular endothelial cells and by macrophages may act as a local regulator of endothelial cells functions and may induce intimal neovascularisation in aortocoronary saphenous vein bypass grafts affected by atherosclerosis.
新生血管形成是长期主动脉冠状动脉大隐静脉旁路移植术的一个显著特征，但此前尚未研究过新生血管形成所涉及的机制。血管内皮生长因子（VEGF）是一种重要的血管生成因子，可诱导内皮细胞迁移和增殖，增强通透性并调节血栓形成。本研究调查了VEGF在主动脉冠状动脉大隐静脉旁路移植术中的表达情况。在再次冠状动脉旁路移植术中，从14例患者身上取出血管造影显示管腔狭窄>75%的主动脉冠状动脉大隐静脉旁路移植血管。这些移植血管表现出两种不同形式的移植血管闭塞：14例移植血管闭塞中有4例（29%）是由于内膜严重增生性改变并伴有附着于退化的管腔内皮的血栓形成；其余的移植血管闭塞（71%）是由于与壁血栓形成相关的动脉粥样硬化病变的发展。增生性改变的内膜段几乎没有新生血管形成，而动脉粥样硬化样病变则含有不规则分布于各处的新生血管。内膜新生血管仅位于富含表达VEGF细胞的微区，此外，新生血管内皮细胞本身也显示VEGF免疫阳性。双重免疫染色显示，在新生血管形成区域，绝大多数巨噬细胞（CD68+）表达VEGF。一些围绕新生血管分支的CD68+泡沫细胞也呈VEGF阳性。这些发现表明，新生血管内皮细胞和巨噬细胞表达的VEGF可能作为内皮细胞功能的局部调节因子，并可能在受动脉粥样硬化影响的主动脉冠状动脉大隐静脉旁路移植术中诱导内膜新生血管形成。
