ANGIOGENIC GROWTH FACTORS OF CORONARY ARTERIAL LESIONS IN KAWASAKI DISEASE AND GENE THERAPY

本研究的目的是：1)探讨川崎病冠脉病变远期血管生成情况，2)评价冠状动脉病变血管生成与病变进展或消退的关系，3)推测血管生成基因治疗的可能性。首先，我们测定了血管内皮生长因子(VEGF)和肝细胞生长因子(HGF)在冠状动脉循环不同部位的血浆浓度，并探讨了这些血管生长因子的分布。结果显示，川崎病急性期血浆血管内皮生长因子和肝细胞生长因子水平显著升高。其次，我们评估了血管内皮功能与血浆中血管内皮生长因子或肝细胞生长因子浓度的关系。冠状动脉内直接注入消心痛(内皮非依赖性血管扩张剂)或乙酰胆碱(内皮依赖性血管扩张剂)，数字化冠状动脉造影术测定血管内皮功能。测量注射血管扩张剂前后冠状动脉内径，计算冠状动脉内径变化率。并探讨血管内皮功能与血浆WEGF、HGF浓度的相关性。再次，用川崎病尸检标本对血管壁进行免疫组织病理学评价。这些原始结果可以作为未来基因治疗该疾病长期冠状动脉异常的重要基础数据。

The objective of this study was 1) to investigate of the angiogenesis in the long-term coronary lesions of Kawasaki disease, 2) to evaluate the relationship between the angiogenesis of coronary lesions and its progression or regression, 3) to speculate of the possibilities of gene therapy of angiogenesis.At first, we measured plasma concentration of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in the various sites of coronary circulation, and investigated the distribution of these angiogenic growth factors. As results, plasma concentration of VEGF and HGF were significantly increased at the acute stage of Kawasaki disease. Additionally, these elevated plasma concentrations were more significantly increased in cases with coronary artery lesions.Secondary, we evaluated the relationship between vascular endothelial function and plasma concentration of VEGF or HGF. Vascular endothelial function was measured by digitalized coronary angiography using the direct infusion of isosorbide dinitrate (endothelial non dependent vasodilator) or acetylcholine (endothelial dependent vasodilator) into the coronary artery. The diameter of coronary artery before and after the infusion of these vasodilator was measured and percent change of coronary diameter was calculated. The correlation between vascular endothelial function and plasma concentration of WEGF or HGF was also investigated. Thirdly, immunohistopathological evaluation of vascular wall was done using autopsy specimen of Kawasaki disease. These primitive results can contribute as an important basic data of coming gene therapy for long-term coronary abnormalities in this disease.