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Observational Study
. 2017 Dec;38(8):1606-1612.
doi: 10.1007/s00246-017-1703-9. Epub 2017 Aug 18.

Interleukin 1 Receptor-Like 1 Protein (ST2) is a Potential Biomarker for Cardiomyopathy in Duchenne Muscular Dystrophy

Julia Anderson  1 , Haeri Seol  1 , Heather Gordish-Dressman  1 , Yetrib Hathout  1 , Christopher F Spurney  2   3 ; CINRG Investigators
Collaborators, Affiliations
Observational Study

Interleukin 1 Receptor-Like 1 Protein (ST2) is a Potential Biomarker for Cardiomyopathy in Duchenne Muscular Dystrophy

Julia Anderson et al. Pediatr Cardiol. 2017 Dec.

Abstract

Duchenne muscular dystrophy (DMD) is a rare, fatal X-linked disorder characterized by the lack of dystrophin, a key sarcolemma muscle protein. Cardiac failure is a significant cause of death in DMD subjects. The purpose of our research was to identify potential cardiac serum biomarkers associated with DMD cardiomyopathy. This is an observational, case-controlled study using subjects from the CINRG DMD natural history study with cardiomyopathy (ejection fraction (EF) <55%; shortening fraction (SF) <28%), subjects without cardiomyopathy (EF ≥ 55%; SF ≥ 28%) compared to normal healthy volunteer subjects. The DMD with cardiomyopathy group had significantly lower average EF and SF (EF = 45 ± 10/SF = 25 ± 2%) than the DMD without cardiomyopathy group (EF = 58 ± 5% and SF = 32 ± 3%; p < 0.01). Among a selected set of potential biomarkers for cardiomyopathy (MMP9, BNP, GAL3, CRP, LEP, TNC, TLR4 and ST2) we validated ST2 as significantly elevated in the serum of DMD cardiomyopathy group (35,798 ± 4884 pg/mL) compared to normal controls (9940 ± 2680 pg/mL; p < 0.01; n = 6). Matrix metallopeptidase 9 (MMP9) levels were found significantly increased in both DMD groups compared to controls (p < 0.01). No significant differences were seen in BNP, GAL3, CRP, LEP, TNC or TLR4 levels. Increased ST2 levels were found in serum of DMD subjects compared to healthy volunteers and further elevated in DMD subjects with cardiomyopathy. Future studies correlating cardiomyopathy with ST2 levels may allow for improved non-invasive monitoring of cardiac disease in DMD subjects.

Keywords: Biomarkers; Cardiomyopathy; Duchenne muscular dystrophy; ST2.

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Conflict of interest statement

Conflict of Interest: Julia Andersen declares that she has no conflict of interest. Haeri Seol declares that she has no conflict of interest. Heather Gordish-Dressman declares that she has no conflict of interest. Yetrib Hathout declares that he has no conflict of interest. Christopher Spurney declares that he has no conflict of interest.

Figures

Figure 1:
Figure 1:. ST2 Serum Levels of DMD with cardiomyopathy, DMD without cardiomyopathy and control groups from ELISA testing.
Serum ST2 levels are significantly greater in DMD subjects with cardiomyopathy than in normal controls. The dots represent data points outside of 1.5 times the inter-quartile range. *p<0.01 compared to the normal control group.
Figure 2:
Figure 2:. ST2 Serum Levels. Linear regression analysis showed that overall serum ST2 levels increase with age in DMD and normal controls.
The DMD with cardiomyopathy group showed a statistically significant difference in ST2 levels compared to normal controls over all ages (p=0.024).
Figure 3:
Figure 3:. MMP9 Serum Levels of DMD with cardiomyopathy, DMD without cardiomyopathy and normal control groups from ELISA testing.
Serum MMP9 levels are significantly greater in DMD subjects than normal controls. The dots represent data points outside of 1.5 times the inter-quartile range. *p<0.01 compared to normal controls.
Figure 4:
Figure 4:. MMP9 Serum Levels. Linear regression analysis showed that overall serum MMP9 levels increase with age in DMD and normal controls.
The DMD with cardiomyopathy and the DMD without cardiomyopathy groups showed a statistically significant difference in logMMP9 levels compared to normal controls over all ages (p=0.006 and p=0.005, respectively.
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Comment in

References

    1. Le Rumeur E (2015) Dystrophin and the two related genetic diseases, Duchenne and Becker muscular dystrophies. Bosn J Basic Med Sci 15: 14–20 - PMC - PubMed
    1. Verhaert D, Richards K, Rafael-Fortney JA, Raman SV (2011) Cardiac involvement in patients with muscular dystrophies: magnetic resonance imaging phenotype and genotypic considerations. Circ Cardiovasc Imaging 4: 67–76 - PMC - PubMed
    1. Spurney CF, McCaffrey FM, Cnaan A, Morgenroth LP, Ghelani SJ, Gordish-Dressman H, Arrieta A, Connolly AM, Lotze TE, McDonald CM, Leshner RT, Clemens PR (2015) Feasibility and Reproducibility of Echocardiographic Measures in Children with Muscular Dystrophies. J Am Soc Echocardiogr 28: 999–1008 - PMC - PubMed
    1. Soslow JH, Damon BM, Saville BR, Lu Z, Burnette WB, Lawson MA, Parra DA, Sawyer DB, Markham LW (2015) Evaluation of post-contrast myocardial t1 in duchenne muscular dystrophy using cardiac magnetic resonance imaging. Pediatr Cardiol 36: 49–56 - PMC - PubMed
    1. Ohlendieck K (2013) Proteomic identification of biomarkers of skeletal muscle disorders. Biomark Med 7: 169–186 - PubMed

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