Coronary Artery Aneurysm Induced by Kawasaki Disease in Children Show Features Typical Senescence

Abstract

Kawasaki disease (KD) causes coronary artery disease (CAD) in children. In addition, a history of KD is suspected to be a risk factor for the development of atherosclerotic heart disease in the future. Histological senescence changes are a common denominator in atherosclerotic lesions in adults, so the present study investigated whether histological senescence changes had already occurred in KD aneurysm. KD coronary aneurysms and internal mammary arteries retrieved from 5 children with KD (3, 4, 5, 6, and 11 years old, respectively) who underwent coronary artery bypass grafting, as well as giant coronary aneurysm size-reducing operations, were analyzed. Senescence-associated strong beta-galactosidase activity was observed in KD aneurysms, but not in the internal mammary arteries. An immunohistochemical analysis of the KD aneurysm using anti-CD31, anti-endothelial nitric oxide synthetase (eNOS), anti-vascular adhesion molecule-1 (VCAM-1), and anti-monocyte chemoattractant protein-1 (MCP-1) showed vascular endothelium CD31 staining, decreased staining of eNOS and strong staining of MCP-1 and VCAM-1. cDNA microarray gene expression profiling revealed increased MCP-1 expression in the KD aneurysm, a finding confirmed by quantitative polymerase chain reaction. Histological features of senescence and active remodeling gene expression show that the KD aneurysm is not a silent vasculitis terminal. The future fate of KD aneurysms, including atherosclerosis, should be monitored carefully.