Fujito Numano1, Chisato Shimizu2, Susan Jimenez-Fernandez2, Matthew Vejar3, Toshiaki Oharaseki4, Kei Takahashi4, Andrea Salgado2, Adriana H Tremoulet5, John B Gordon6, Jane C Burns5, Lori B Daniels3. 1. Departments of Pediatrics, University of California, San Diego School of Medicine, USA. Electronic address: fnumano@ucsd.edu. 2. Departments of Pediatrics, University of California, San Diego School of Medicine, USA. 3. Departments of Medicine, University of California, San Diego School of Medicine, USA. 4. Toho University Ohashi Medical Center, Department of Pathology, Tokyo, Japan. 5. Departments of Pediatrics, University of California, San Diego School of Medicine, USA; Rady Children's Hospital San Diego, USA. 6. San Diego Cardiac Center and Sharp Memorial Hospital, San Diego, CA, USA.
Abstract
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-β 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.
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-β 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.
Authors: Shinsuke Hoshino; Sonia Jain; Chisato Shimizu; Samantha Roberts; Feng He; Lori B Daniels; Andrew M Kahn; Adriana H Tremoulet; John B Gordon; Jane C Burns Journal: Int J Cardiol Heart Vasc Date: 2021-09-01