Abstract
This study aimed to develop innovative therapy to prevent obstructive coronary arterial lesions in Kawasaki disease (KD). We studied fundamental mechanisms related to arteritis in acute phase and remodeling of the arteries in convalescent and late phase. We examined formalin-fixed specimens of coronary arteries from 18 patients with KD by immunohistochemical staining. We used antibodies against various vascular growth factors, including TGFβ1, PDGF-A, bFGF, VEGF and their receptors. We also used cell type-specific antibodies to CD68, CD34, factor VIII and α-actin. In acute phase (15th day of illness), severe edema and inflammatory cell infiltration were observed in the arteries, especially in the area from adventitia to intima. In convalescent phase (2.5-12.5 months after onset), we observed synthesis of loose gelatinous extra-cellular matrix (ECM) that leads to intimal thickening and occlusion of aneurysmal lumen. Inflammatory cells, such as iNOS+ cells, VEGF+ cells, and CD68+ macrophages, infiltrated in the ECM of subendothelial layer and deep intima by one year after onset of KD. Among the infiltrating cells, a large number of CD34+ cells, Tie2+ cells and KDR+ cells, known as endothelial progenitor cells (EPCs), were seen to migrate from adventitia to deep intima. In the later convalescent phase, the loose gelatinous ECM was replaced by smooth muscle cells (SMCs) and collagen fibers. In late phase (2.5-19 years after onset), the growth factors were strongly expressed in proliferating SMCs of progressively thickening intima. In conclusion, this study indicated that the remodeling of coronary arteries begins with synthesis of ECM in the intima and cellular infiltration. Thereafter, vascularization, remarkable proliferation of SMCs and fibrosis are occurred in order. In addition, it became obvious the remarkable vascularization in KD depends on not only angiogenesis but also postnatal vasculogenesis that was proved by infiltration of a large number of EPCs.
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Suzuki, A., Miyagawa-Tomita, S., Nakazawa, M. et al. Coronary Arteritis and Arterial Remodeling in Kawasaki Disease: Immunohistochemical Study. Pediatr Res 53, 173 (2003). https://doi.org/10.1203/00006450-200301000-00119
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DOI: https://doi.org/10.1203/00006450-200301000-00119