Kawasaki Disease-like Vasculitis Facilitates Atherosclerosis, and Statin Shows a Significant Antiatherosclerosis and Anti-Inflammatory Effect in a Kawasaki Disease Model Mouse

川崎病样血管炎促进动脉粥样硬化形成,他汀类药物在川崎病模型小鼠中表现出显著的抗动脉粥样硬化和抗炎作用

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作者:Yusuke Motoji, Ryuji Fukazawa, Ryosuke Matsui, Noriko Nagi-Miura, Yasuo Miyagi, Yasuhiko Itoh, Yosuke Ishii

Abstract

Kawasaki disease (KD) is an acute form of systemic vasculitis that may promote atherosclerosis in adulthood. This study examined the relationships between KD, atherosclerosis, and the long-term effects of HMG-CoA inhibitors (statins). Candida albicans water-soluble fraction (CAWS) was injected intraperitoneally into 5-week-old male apolipoprotein-E-deficient (Apo E-/-) mice to create KD-like vasculitis. Mice were divided into 4 groups: the control, CAWS, CAWS+statin, and late-statin groups. They were sacrificed at 6 or 10 weeks after injection. Statin was started after CAWS injection in all groups except the late-statin group, which was administered statin internally 6 weeks after injection. Lipid plaque lesions on the aorta were evaluated with Oil Red O. The aortic root and abdominal aorta were evaluated with hematoxylin and eosin staining and immunostaining. CAWS vasculitis significantly enhanced aortic atherosclerosis and inflammatory cell invasion into the aortic root and abdominal aorta. Statins significantly inhibited atherosclerosis and inflammatory cell invasion, including macrophages. CAWS vasculitis, a KD-like vasculitis, promoted atherosclerosis in Apo E-/- mice. The long-term oral administration of statin significantly suppressed not only atherosclerosis but also inflammatory cell infiltration. Therefore, statin treatment may be used for the secondary prevention of cardiovascular events during the chronic phase of KD.

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