Molecular mechanisms of endothelial dysfunction in Kawasaki-disease-associated vasculitis

Abstract

Kawasaki disease (KD) is an acute, inflammation mediated vasculitis, mainly affecting in children under five, which is consider as the most common coronary artery disease in children. The injuries of coronary arteries would result in dilation or thrombus formation, bringing great threaten to patients. Endothelium, located in the inner surface of coronary artery, serves as the interface between the circulating inflammatory cells and vascular media or adventitia, which is the first target of inflammatory attacks during early stage of KD. A series of studies have determined vascular endothelial cells damages and dysfunction in KD patients. However, current therapeutic strategy is still challenging. So that it is critical to underline the mechanisms of endothelium injuries. In this review, the role of endothelial cells in the pathogenesis of KD and the therapeutic methods for endothelial cells were systematically described.

Keywords: Kawasaki disease; coronary artery disease; endothelial cells; inflammation; molecular mechanisms.

Figure 1

Pathway of cytokine production and inflammatory cell-endothelial cell interaction in KD. HMGB1 up-regulated NF-κB-mediated inflammatory responses and promoted IL1β and TNFα production. IL37 induced apoptosis and inflammation of endothelial cells through the IL-1R8 pathway. VEGF activated Ca2+/NFAT pathway induced inflammation activity by regulating E-selectin, VCAM-1 and MCP-1. Monocyte-produced VEGF also took part in cell migration. Sema4D released by Neutrophil affected endothelial cell cytokine production. Monocytes, macrophage, platelets, and granulocytes recruited to coronary artery and adhesion endothelial cells.