Plasma profiling determinants of matrix homeostasis in paediatric dilated cardiomyopathy.
OBJECTIVE
Dilated cardiomyopathy is an important cause of cardiac failure in both children and adults, but is more progressive in children. In adult dilated cardiomyopathy, left ventricular remodelling is associated with changes in the plasma levels of matrix metalloproteinases and tissue inhibitor of metalloproteinases. Plasma matrix metalloproteinases and tissue inhibitors of metalloproteinase changes in paediatric dilated cardiomyopathy have not been examined. This study developed a low blood volume, high-sensitivity assay to test the hypothesis that unique and differential plasma matrix metalloproteinases and tissue inhibitors of metalloproteinase profile exist in patients with paediatric dilated cardiomyopathy.


RESULTS
A systemic blood sample (1 millilitre) was obtained from seven children aged 8 plus or minus 7 years with dilated cardiomyopathy and 26 age-matched normal volunteers. Using a high-throughput multiplex suspension immunoassay, plasma levels were quantified for collagenases (matrix metalloproteinase-8), gelatinases (matrix metalloproteinase-2 and -9), lysins (matrix metalloproteinase-3 and -7), and tissue inhibitor of metalloproteinases-1, -2, and -4. The matrix metalloproteinase to tissue inhibitors of metalloproteinases ratios were also calculated. The plasma matrix metalloproteinase-2, -7, -8, and -9 levels were increased by greater than twofold in patients with dilated cardiomyopathy than normal patients (with p less than 0.05). Patients with dilated cardiomyopathy also had significantly higher tissue inhibitors of metalloproteinases-1 and -4 (298% and 230%; with p less than 0.05).


CONCLUSIONS
These unique findings show that a specific plasma matrix metalloproteinase/tissue inhibitor of metalloproteinase profile occurs in paediatric dilated cardiomyopathy when compared to the cases of normal children. These distinct differences in the determinants of myocardial matrix structure and function may contribute to the natural history of dilated cardiomyopathy in children and may provide a novel biomarker platform in paediatric dilated cardiomyopathy.
Department of Surgery, Division of Cardiothoracic Surgery, Veterans Affairs Medical Center, Medical University of South Carolina, Charleston, South Carolina, USA.
Tain-Yen
TY
Hsia
Jeremy M
JM
Ringewald
Robert E
RE
Stroud
Nadia
N
Roessler
Nidhi
N
Kumar
Scott T
ST
Reeves
Francis G
FG
Spinale
D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002311:Cardiomyopathy, Dilated / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007223:Infant; D020782:Matrix Metalloproteinases / Q000097:blood*; D011379:Prognosis; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*
D015415:Biomarkers; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases