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

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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.