Yamamura Mitsuhiro
Department of Cardiovascular Surgery, Hyogo Medical University, Nishinomiya-city, Hyogo, Japan.
Int J Angiol. 2024 Feb 5;33(3):135-138. doi: 10.1055/s-0044-1779300. eCollection 2024 Sep.
Postoperative intimal hyperplasia is the major cause of the vein graft occlusion. It is very important to establish an animal model for the start of research. After my vascular surgery residency in Japan, I started my research work on postoperative intimal hyperplasia at the University of Wisconsin-Madison. My research showed that endothelial injury and monocyte infiltration is the key for postoperative intimal hyperplasia, which is very similar to Ross' pathogenesis of atherosclerosis as an inflammatory disease. Focusing on postoperative intimal hyperplasia as an inflammatory disease, especially on tumor necrosis factor-α, FR-167653 (tumor necrosis factor-α suppressive agent, inhibitor of 38 mitogen-activated protein kinase; Fujisawa Pharmaceutical Co., Ltd., Japan) is found to suppress postoperative intimal hyperplasia in a rat model by reducing serum monocyte chemoattractant protein-1 levels. However, FR-167653 is not commercially available today. Because endothelial injury is the first step of postoperative intimal hyperplasia, I investigated whether the free radical scavenger, edaravone (Radicut, Mitsubishi Tanabe Pharma Co., Japan), which alleviates the endothelial injury , can also suppress postoperative intimal hyperplasia. Moreover, the free radical scavenger edaravone (Radicut®, Mitsubishi Tanabe Pharma Co.) is also found to suppress postoperative intimal hyperplasia, by alleviating endothelial injury. In clinical settings, it is very important to detect postoperative intimal hyperplasia before its establishment. Hepatocyte growth factor is not only a hepatic growth factor but also a vascular endothelial growth factor. Recently, serum hepatocyte growth factor level was found to be a candidate biomarker for postoperative intimal hyperplasia in our rat model.
术后内膜增生是静脉移植物闭塞的主要原因。建立动物模型对于开展研究至关重要。我在日本完成血管外科住院医师培训后，开始在威斯康星大学麦迪逊分校开展关于术后内膜增生的研究工作。我的研究表明，内皮损伤和单核细胞浸润是术后内膜增生的关键，这与罗斯提出的动脉粥样硬化作为一种炎症性疾病的发病机制非常相似。聚焦于作为炎症性疾病的术后内膜增生，尤其是针对肿瘤坏死因子-α，发现FR-167653（肿瘤坏死因子-α抑制剂，丝裂原活化蛋白激酶38抑制剂；日本藤泽制药有限公司）通过降低血清单核细胞趋化蛋白-1水平，可抑制大鼠模型中的术后内膜增生。然而，FR-167653如今已无商业供应。由于内皮损伤是术后内膜增生的第一步，我研究了能减轻内皮损伤的自由基清除剂依达拉奉（Radicut，日本三菱田边制药公司）是否也能抑制术后内膜增生。此外，还发现自由基清除剂依达拉奉（Radicut®，三菱田边制药公司）通过减轻内皮损伤，也能抑制术后内膜增生。在临床环境中，在术后内膜增生形成之前进行检测非常重要。肝细胞生长因子不仅是一种肝脏生长因子，也是一种血管内皮生长因子。最近，在我们的大鼠模型中发现血清肝细胞生长因子水平是术后内膜增生的一个候选生物标志物。
