Friedl Reinhard, Li Jun, Schumacher Bernd, Hanke Hartmut, Waltenberger Johannes, Hannekum Andreas, Stracke Sylvia
Department of Cardiac Surgery, University Hospital Ulm, Ulm, Germany.
Ann Thorac Surg. 2004 Oct;78(4):1312-8. doi: 10.1016/j.athoracsur.2004.02.066.
The development of fibromuscular intimal hyperplasia and subsequent graft failure remains an urgent problem in cardiac surgery. Transforming growth factor-beta1 (TGF-beta1) is involved in the pathogenesis of arteriosclerosis through induction of extracellular matrix proteins. We tested the hypothesis that intimal hyperplasia is already present in human saphenous veins and left internal mammary arteries before coronary artery bypass surgery and is associated with an increased expression of TGF-beta1.
Forty-six segments of saphenous veins and 27 of left internal mammary arteries were collected from 50 patients undergoing coronary artery bypass surgery. Morphometric analysis was performed by microscopic computer analysis. Immunohistochemistry was performed with antibodies directed against TGF-beta1, its latent binding protein (LTBP-1) and its type 2 receptor (RII).
The incidence of intimal hyperplasia was significantly higher in saphenous veins (67.4%) than in mammary arteries (29.6%; p < 0.05). Saphenous veins and mammary arteries with intimal hyperplasia expressed more TGF-beta1 (endothelial and intimal layers) and LTBP-1 (intimal and medial layers) when compared with corresponding vessels without hyperplasia (both groups p < 0.05). Endothelial and intimal RII expression was significantly higher in saphenous veins with intimal hyperplasia as compared with saphenous veins without hyperplasia (p < 0.05). Transforming growth factor-beta1 staining in the intima correlated with the presence of an intimal hyperplasia in saphenous veins (rho = 0.317) and mammary arteries (rho = 0.428).
Local TGF-beta1 expression is associated with the presence of intimal hyperplasia in the examined vessels. Preexisting intimal hyperplasia is more prevalent and serious in saphenous veins than in left internal mammary arteries, giving further explanation to the superior long-term results of left internal mammary grafts.
纤维肌性内膜增生的发展及随后的移植物失败仍是心脏外科手术中一个亟待解决的问题。转化生长因子-β1（TGF-β1）通过诱导细胞外基质蛋白参与动脉粥样硬化的发病机制。我们检验了这样一个假设，即内膜增生在冠状动脉搭桥手术前就已存在于人类大隐静脉和左乳内动脉中，且与TGF-β1表达增加有关。
从50例行冠状动脉搭桥手术的患者身上采集了46段大隐静脉和27段左乳内动脉。通过显微镜计算机分析进行形态计量分析。使用针对TGF-β1、其潜在结合蛋白（LTBP-1）及其2型受体（RII）的抗体进行免疫组织化学检测。
大隐静脉内膜增生的发生率（67.4%）显著高于乳内动脉（29.6%；p<0.05）。与无增生的相应血管相比，有内膜增生的大隐静脉和乳内动脉表达更多的TGF-β1（内皮和内膜层）和LTBP-1（内膜和中层）（两组p<0.05）。与无内膜增生的大隐静脉相比，有内膜增生的大隐静脉内皮和内膜RII表达显著更高（p<0.05）。内膜中TGF-β1染色与大隐静脉（rho=0.317）和乳内动脉（rho=0.428）内膜增生的存在相关。
局部TGF-β1表达与所检查血管内膜增生的存在有关。大隐静脉中预先存在的内膜增生比左乳内动脉更普遍、更严重，这进一步解释了左乳内动脉移植物更好的长期效果。
