title: Evaluation of Proinflammatory Prognostic Biomarkers for Fabry Cardiomyopathy With Enzyme Replacement Therapy.
abstract: Fabry disease (FD) causes progressive glycosphingolipid accumulation and damage in various organs, and several proinflammatory processes may be involved in this disease. Enzyme replacement therapy (ERT) can reduce the severity of Fabry cardiomyopathy (FC), but whether ERT could attenuate proinflammatory cytokines in FC remains unclear. In this study, we attempted to evaluate the efficacy of ERT on proinflammatory cytokines and vascular cell adhesion biomarkers.
  
  
  
  We enrolled 25 patients with FC and administered ERT to them according to the present clinical guideline. We analyzed and compared echocardiographic and blood examination results between 25 patients with FD without left ventricular hypertrophy (LVH), 25 patients with FC with LVH who were receiving ERT, and 25 healthy age- and sex-matched controls. The parameters of cardiac function at baseline and 12 months after ERT were assessed through echocardiography, and the expression profiles of proinflammatory biomarkers were determined.
  
  
  
  Left ventricular mass (LVM), LVM index (LVMI), interventricular septal thickness at diastole, and serum levels of globotriaosylsphingosine (Gb3) were elevated in patients with FC. Meanwhile, several proinflammatory cytokines, including interleukin (IL)-6, IL-2, IL-1b, tumor necrosis factor-α, intercellular adhesion molecule, soluble vascular cell adhesion molecule, and monocyte chemoattractant protein-1 (MCP-1) were concomitantly increased. ERT significantly reduced these transthoracic echocardiographic parameters and lyso-Gb3 and proinflammatory cytokine levels. The changes in IL-6, MCP-1, and lyso-Gb3 levels were positively correlated with the change in LVMI.
  
  
  
  Our study has revealed that proinflammatory biomarkers, particularly IL-6 and MCP-1, may represent effective biomarkers for evaluating ERT outcomes in patients with FC.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kuan-Hsuan
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yueh
authors.initials: Y
authors.lastname: Chien
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Divison of Cardiology and Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Kang-Ling
authors.initials: KL
authors.lastname: Wang
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Health Care and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan; Divison of Cardiology and Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hsin-Bang
authors.initials: HB
authors.lastname: Leu
authors.affiliation: Department of Surgery, National Yang-Ming University Hospital, Taipei, Taiwan.
authors.forename: Chen-Yuan
authors.initials: CY
authors.lastname: Hsiao
authors.affiliation: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ying-Hsiu
authors.initials: YH
authors.lastname: Lai
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chien-Ying
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yuh-Lih
authors.initials: YL
authors.lastname: Chang
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Divison of Cardiology and Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Pediatrics, Taipei, Veterans General Hospital, Taipei, Taiwan.
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Divison of Cardiology and Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: wcyu@vghtpe.gov.tw.
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Yu
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D004452:Echocardiography; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000150:complications / Q000628:therapy*; D005260:Female; D006017:Glycolipids / Q000097:blood; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000209:etiology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013107:Sphingolipids / Q000097:blood; D000519:alpha-Galactosidase / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006017:Glycolipids; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid; D000519:alpha-Galactosidase