title: Extracellular matrix turnover and disease severity in Anderson-Fabry disease.
abstract: BACKGROUND
  Anderson-Fabry Disease (AFD) is an inherited metabolic disease associated with premature death secondary to cardiovascular and renal disease. Patients with AFD develop progressive left ventricular (LV) remodelling and heart failure. We hypothesized that altered extracellular matrix (ECM) turnover contributes to the pathophysiology of cardiac disease in AFD.
  
  
  RESULTS
  Twenty-nine consecutive patients (44.1 +/- 11.7 years, 15 male) with AFD and 21 normal controls (39.7 +/- 11.3 years, 10 male) had serum analysed for matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix metalloproteinase-1 and -2 (TIMP-1, TIMP-2). All patients underwent clinical assessment, echocardiography and Mainz Severity Score Index (MSSI) measurement, a validated severity score in AFD. MMP-9 levels were significantly higher in patients than controls (1003.8 +/- 337.8 ng/ml vs 576.7 +/- 276.3 ng/ml respectively, p < 0.001). There were no differences in TIMP levels between patients and controls. There was a positive correlation between MMP-9 levels and MSSI (r = 0.5, p = 0.01). There was a negative correlation between MMP-9 and endocardial fractional shortening (FS) (r = -0.5, p = 0.01) and mid-wall FS (r = -0.6, p = 0.001). There was no correlation between other echocardiographic parameters and MMP-9 levels. These relations were independent of age and sex using stepwise linear regression analysis.
  
  
  CONCLUSIONS
  Patients with AFD have abnormal ECM turnover compared to normal controls. The correlation between MMP-9 levels and systolic function suggests that altered ECM turnover is important in cardiac remodelling. The association between MMP-9 and overall disease severity suggests that circulating levels of MMP-9 may provide a useful marker for assessing the response of patients with AFD to enzyme replacement treatment.
authors.affiliation: The Heart Hospital, UCL, London, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Shah
authors.forename: D A
authors.initials: DA
authors.lastname: Hughes
authors.forename: M H
authors.initials: MH
authors.lastname: Tayebjee
authors.forename: R J
authors.initials: RJ
authors.lastname: MacFadyen
authors.forename: A B
authors.initials: AB
authors.lastname: Mehta
authors.forename: P M
authors.initials: PM
authors.lastname: Elliott
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004699:Endocardium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D000795:Fabry Disease / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009154:Mutation; D012044:Regression Analysis; D012737:Sex Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020780:Matrix Metalloproteinase 9