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Plasma profiling determinants of matrix homeostasis in paediatric dilated cardiomyopathy

Published online by Cambridge University Press:  27 October 2010

Tain-Yen Hsia ,
Jeremy M. Ringewald ,
Robert E. Stroud ,
Nadia Roessler ,
Nidhi Kumar ,
Scott T. Reeves  and
Francis G. Spinale
Tain-Yen Hsia
Affiliation:
Department of Surgery, Division of Cardiothoracic Surgery, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
Jeremy M. Ringewald
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
Robert E. Stroud
Affiliation:
Department of Surgery, Division of Cardiothoracic Surgery, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
Nadia Roessler
Affiliation:
Department of Surgery, Division of Cardiothoracic Surgery, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
Nidhi Kumar
Affiliation:
Department of Surgery, Division of Cardiothoracic Surgery, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
Scott T. Reeves
Affiliation:
Department of Anesthesia and Perioperative Medicine, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
Francis G. Spinale*
Affiliation:
Department of Surgery, Division of Cardiothoracic Surgery, Veterans Affairs Medical Center, Medical University of South Carolina and the Ralph H. Johnson, Charleston, South Carolina, United States of America
*
Correspondence to: F. G. Spinale, MD, PhD, Cardiothoracic Surgery, Strom Thurmond Research Center, 114 Doughty Street, Suite 625, Charleston, South Carolina 29425, United States of America. Tel: (843) 876 5186; Fax: (843) 876 5187; E-mail: wilburnm@musc.edu
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Abstract

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.

Methods/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.

Keywords

Cardiac failureremodellingplasmamyocardialbiomarker
Type
Original Articles
Information
Cardiology in the Young , Volume 21 , Issue 1 , February 2011 , pp. 52 - 61
Copyright
Copyright © Cambridge University Press 2010

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