Kawasaki disease (KD) is an acute inflammatory disorder of children frequently associated with the development of coronary artery abnormalities. Although a gr eat deal is known about inflammatory and immune responses ...Kawasaki disease (KD) is an acute inflammatory disorder of children frequently associated with the development of coronary artery abnormalities. Although a gr eat deal is known about inflammatory and immune responses in acute KD, the mecha nisms linking the immune response to vascular changes are not known. To gain fur ther insight into this process, we performed a microarray gene expression analys is on RNA isolated from the peripheral blood mononuclear cells of four patients with KD during both their acute and convalescent phases. Fortyseven genes of 712 9 genes examined showed an increased expression in three or all four patients in the acute compared with the convalescent phase of KD. Fourteen of these genes w ere significantly (p < 0.05) up-regulated, including several inflammatory resp onse genes (e. g. S-100 A9 protein) and also anti-inflammatory genes (e. g. TS G-6). Of greatest interest, the adrenomedullin (ADM) gene, known to be associat ed with coronary artery vasodilation, was up-regulated in the acute phase of KD (p = 0.024). Up-regulation of ADM in the acute phase of KD was confirmed in p eripheral blood mononuclear cells of 11 additional KD patients by reverse transc riptase-PCR (p < 0.01). Isolated blood monocytes but not lymphocytes were demo nstrated by real-time PCR to have increased ADM mRNA (p = 0.01). Plasma ADM pr otein level in 32 additional KD patients was also confirmed to be higher in acut e KD compared with convalescent KD (p < 0.032). It is interesting that from mic roarray results, other molecules known to be associated with coronary dilation, including nitric oxide, prostacyclin, acetylcholine, bradykinin, substance P, an d serotonin, were not elevated in acute KD. Our current study suggests that ADMe xpressing monocytes that infiltrate the coronary vascular wall may be the cause of coronary dilation in the acute phase of KD.展开更多
文摘Kawasaki disease (KD) is an acute inflammatory disorder of children frequently associated with the development of coronary artery abnormalities. Although a gr eat deal is known about inflammatory and immune responses in acute KD, the mecha nisms linking the immune response to vascular changes are not known. To gain fur ther insight into this process, we performed a microarray gene expression analys is on RNA isolated from the peripheral blood mononuclear cells of four patients with KD during both their acute and convalescent phases. Fortyseven genes of 712 9 genes examined showed an increased expression in three or all four patients in the acute compared with the convalescent phase of KD. Fourteen of these genes w ere significantly (p < 0.05) up-regulated, including several inflammatory resp onse genes (e. g. S-100 A9 protein) and also anti-inflammatory genes (e. g. TS G-6). Of greatest interest, the adrenomedullin (ADM) gene, known to be associat ed with coronary artery vasodilation, was up-regulated in the acute phase of KD (p = 0.024). Up-regulation of ADM in the acute phase of KD was confirmed in p eripheral blood mononuclear cells of 11 additional KD patients by reverse transc riptase-PCR (p < 0.01). Isolated blood monocytes but not lymphocytes were demo nstrated by real-time PCR to have increased ADM mRNA (p = 0.01). Plasma ADM pr otein level in 32 additional KD patients was also confirmed to be higher in acut e KD compared with convalescent KD (p < 0.032). It is interesting that from mic roarray results, other molecules known to be associated with coronary dilation, including nitric oxide, prostacyclin, acetylcholine, bradykinin, substance P, an d serotonin, were not elevated in acute KD. Our current study suggests that ADMe xpressing monocytes that infiltrate the coronary vascular wall may be the cause of coronary dilation in the acute phase of KD.
