Plasma profiling determinants of matrix homeostasis in paediatric dilated cardiomyopathy

Abstract

Objective Dilated cardiomyopathy is an important cause of heart failure in both children and adults, but is more progressive in children. In adult dilated cardiomyopathy, left ventricular remodeling is associated with changes in plasma levels of matrix metalloproteinases, and tissue inhibitor of metalloproteinases. Plasma matrix metalloproteinases, and tissue inhibitors of metalloproteinase changes in pediatric dilated cardiomyopathy has not been examined. The present 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 exists in pediatric dilated cardiomyopathy patients. Methods/Results A systemic blood sample (1 milliliter) was obtained from 7 children with dilated cardiomyopathy (age 8 plus or minus 7 years), 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, -9), lysins (matrix metalloproteinase-3, -7), and tissue inhibitor of metalloproteinases-1, -2, and -4. Matrix metalloproteinase to tissue inhibitor of metalloproteinases ratios were also calculated. Plasma matrix metalloproteinase-2, -7, -8 and -9 levels were increased by greater than 2-fold in dilated cardiomyopathy patients than normals ( with p less than 0.05). Dilated cardiomyopathy patients also had significantly higher tissue inhibitor of metalloproteinases-1 and -4 (298 percent and 230 percent; with p less than 0.05). Conclusions These unique findings demonstrated that a specific plasma matrix metalloproteinase/tissue inhibitors of metalloproteinase profile occurs in pediatric dilated cardiomyopathy when compared to 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 pediatric dilated cardiomyopathy.

Procollagen type III amino-terminal propeptide: a serum biomarker of left ventricular remodelling in paediatric dilated cardiomyopathy

“…Only one other published study has examined the role of extracellular matrix biomarkers in children with dilated cardiomyopathy. In a study of seven children with idiopathic dilated cardiomyopathy, Hsia et al 31 studied plasma matrix metalloproteinase and tissue inhibitor of metalloproteinase profiles, markers related to extracellular matrix remodelling changes, and compared them with 26 normal children. Their study subjects were similar to our study population in that the majority were minimally symptomatic (71% NYHA Class II), and were a mean of 2.7 ± 1.4 years from initial diagnosis.…”