title: Galectin-3 is a marker of myocardial and vascular fibrosis in Kawasaki disease patients with giant aneurysms.
abstract: BACKGROUND
  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.
  
  
  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: Departments of Pediatrics, University of California, San Diego School of Medicine, USA. Electronic address: fnumano@ucsd.edu.
authors: Fujito
authors: F
authors: Numano
authors: Departments of Pediatrics, University of California, San Diego School of Medicine, USA.
authors: Chisato
authors: C
authors: Shimizu
authors: Departments of Pediatrics, University of California, San Diego School of Medicine, USA.
authors: Susan
authors: S
authors: Jimenez-Fernandez
authors: Departments of Medicine, University of California, San Diego School of Medicine, USA.
authors: Matthew
authors: M
authors: Vejar
authors: Toho University Ohashi Medical Center, Department of Pathology, Tokyo, Japan.
authors: Toshiaki
authors: T
authors: Oharaseki
authors: Toho University Ohashi Medical Center, Department of Pathology, Tokyo, Japan.
authors: Kei
authors: K
authors: Takahashi
authors: Departments of Pediatrics, University of California, San Diego School of Medicine, USA.
authors: Andrea
authors: A
authors: Salgado
authors: Departments of Pediatrics, University of California, San Diego School of Medicine, USA; Rady Children's Hospital San Diego, USA.
authors: Adriana H
authors: AH
authors: Tremoulet
authors: San Diego Cardiac Center and Sharp Memorial Hospital, San Diego, CA, USA.
authors: John B
authors: JB
authors: Gordon
authors: Departments of Pediatrics, University of California, San Diego School of Medicine, USA; Rady Children's Hospital San Diego, USA.
authors: Jane C
authors: JC
authors: Burns
authors: Departments of Medicine, University of California, San Diego School of Medicine, USA.
authors: Lori B
authors: LB
authors: Daniels
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002675:Child, Preschool; D003323:Coronary Aneurysm / Q000097:blood* / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000378:metabolism* / Q000473:pathology; D037502:Galectin 3 / Q000097:blood*; D006801:Humans; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood* / Q000473:pathology; D009205:Myocarditis / Q000097:blood / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D058628:Myofibroblasts / Q000473:pathology; D014652:Vascular Diseases / Q000097:blood / Q000473:pathology*
chemical_list: D015415:Biomarkers; D037502:Galectin 3
keywords: Galectin-3; Giant coronary artery aneurysm; Kawasaki disease; Myocardial fibrosis; Myocarditis