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Extracellular matrix turnover and disease severity in Anderson–Fabry disease

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Summary

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. Methods and 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.

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Abbreviations

AFD:

Anderson-Fabry disease

ECM:

extracellular matrix

FSe :

endocardial fractional shortening

FSm :

mid wall fractional shortening

IVS:

interventricular septum thickness

LV:

left ventricular

LVed:

end-diastolic diameter

LVes:

left ventricular end-systolic diameter

LVH:

left ventricular hypertrophy

LVMI:

LV mass indexed to body surface area

MMPs:

matrix metalloproteinases

MSSI:

Mainz Severity Score Index

MWd:

diastolic midwall thickness

MWs:

systolic midwall thickness

PW:

posterior wall thickness

RWT:

relative wall thickness

TIMPS:

tissue inhibitors of metalloproteinases

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Author information

Authors and Affiliations

  1. The Heart Hospital, UCL, London, UK

    J. S. Shah & P. M. Elliott

  2. The Lysosomal Disorders Unit, The Royal Free Hospital, London, UK

    D. A. Hughes & A. B. Mehta

  3. City Hospital, Dudley Road, Birmingham, UK

    M. H. Tayebjee & R. J. MacFadyen

Authors
  1. J. S. Shah
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  2. D. A. Hughes
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  3. M. H. Tayebjee
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  4. R. J. MacFadyen
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  5. A. B. Mehta
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  6. P. M. Elliott
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Corresponding author

Correspondence to P. M. Elliott.

Additional information

Communicating editor: Robert Desnick

Competing interests: None declared

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Shah, J.S., Hughes, D.A., Tayebjee, M.H. et al. Extracellular matrix turnover and disease severity in Anderson–Fabry disease. J Inherit Metab Dis 30, 88–95 (2007). https://doi.org/10.1007/s10545-006-0360-6

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  • DOI: https://doi.org/10.1007/s10545-006-0360-6

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