Galectin-3 is a marker of myocardial and vascular fibrosis in Kawasaki disease patients with giant aneurysms

INTERNATIONAL JOURNAL OF CARDIOLOGY

卷:201

Article

Numano, Fujito¹  Shimizu, Chisato¹  Jimenez-Fernandez, Susan¹  Vejar, Matthew²  Oharaseki, Toshiaki³  Takahashi, Kei³  Salgado, Andrea¹  Tremoulet, Adriana H.^1,4  Gordon, John B.^5,6  Burns, Jane C.^1,4  Daniels, Lori B.² 

[1] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA

[3] Toho Univ, Ohashi Med Ctr, Dept Pathol, Tokyo, Japan

[4] Katy Childrens Hosp San Diego, San Diego, CA USA

[5] San Diego Cardiac Ctr, San Diego, CA USA

[6] Sharp Mem Hosp & Rehabil Ctr, San Diego, CA USA

关键词: Kawasaki disease;    Galectin-3;    Myocardial fibrosis;    Giant coronary artery aneurysm;    Myocarditis;   

DOI  :  10.1016/j.ijcard.2015.07.063

来源: Elsevier

【 摘 要 】

Backgrounds: Galectin-3 (Gal-3) is a multifunctional matricellular protein associated with heart failure and cardiovascular events. Gal-3 is required for transforming growth factor-beta pathway-mediated myofibroblast activation that is a key process in coronary artery aneurysm formation in Kawasaki Disease (KD). Autopsies from young adults late after KD onset (AKD) have demonstrated bridging fibrosis throughout the myocardium and arteries. In this study, we postulated that Gal-3 may participate in the pathogenesis of myocardial and vascular fibrosis and the remodeling of coronary artery aneurysms following acute KD. Methods and results: We measured plasma Gal-3 levels in 63 pediatric KD (PKD) and 81 AKD subjects. AKD subjects with giant aneurysms had significantly higher Gal-3 levels compared to the other adult groups (all p < 0.05). All PKD groups had significantly higher Gal-3 levels than pediatric healthy controls (HC) (all p < 0.05). Histological and immunohistochemical staining was performed on tissues from 10 KD autopsies and one explanted heart. Gal-3 positive staining was detected associated with acute inflammation and in spindle-shaped cells in the myocardium and arterial wall in KD subjects with giant aneurysms. Conclusions: AKD subjects with giant aneurysms and PKD subjects had significantly higher plasma Gal-3 levels than HC and Gal-3 expression was increased in the myocardium of KD subjects who died with either acute inflammation or marked myocardial fibrosis. Gal-3 may be a clinically useful biomarker that identifies a subset of KD patients at highest risk of myocardial and vascular fibrosis, and may be an attractive therapeutic target to prevent myocardial dysfunction in this subset. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

Free