title: Determinants of extracellular matrix remodelling are differentially expressed in paediatric and adult dilated cardiomyopathy.
abstract: OBJECTIVE
  The left ventricular phenotype of idiopathic dilated cardiomyopathy (DCM) can appear similar in paediatric and adult patients. However, the aetiology of paediatric DCM is usually idiopathic, and often leads an aggressive clinical course. A structural underpinning of DCM is extracellular matrix changes, which are determined by a balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). This study tested the hypothesis that different MMP/TIMP profiles occur in paediatric and adult DCM patients.
  
  
  RESULTS
  Left ventricular samples from paediatric (age 9 ± 5 years; n = 10) and adult (age 62 ± 3 years; n = 20) DCM (at time of transplant) were subjected to an MMP/TIMP multiplex array and immunoassay in order to measure the MMP subclasses; collagenases (MMP-8, -13), gelatinases (MMP-2, -9), stromelysin/matrilysin (MMP-3, -7), membrane type (MT1-MMP), as well as for the four known TIMPs. MMP-8 and -9 levels increased by over 150% (P < 0.05), whereas MMP-3 and -7 levels decreased by over 30% (P < 0.05) in paediatric DCM when compared with adult DCM. TIMP-1 and -2 levels increased two-fold (P < 0.05), but TIMP-3 fell by 41% (P < 0.05) in paediatric DCM. Myocardial levels of specific interleukins (IL-1beta, IL-2, IL-8) were increased by approximately 50% in paediatric DCM.
  
  
  CONCLUSIONS
  These unique findings demonstrated that a specific MMP/TIMP profile occurs in paediatric DCM when compared with adult DCM, and that local cytokine induction may contribute to this process. These distinct differences in the determinants of myocardial matrix structure and function may contribute to the natural history of DCM in children.
authors.affiliation: Division of Cardiothoracic Surgery, Medical University of South Carolina, 114 Doughty Street, Charleston, SC 29403, USA.
authors.forename: Tain-Yen
authors.initials: TY
authors.lastname: Hsia
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Ringewald
authors.forename: Robert E
authors.initials: RE
authors.lastname: Stroud
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Forbus
authors.forename: Scott M
authors.initials: SM
authors.lastname: Bradley
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: Francis G
authors.initials: FG
authors.lastname: Spinale
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
chemical_list: D016207:Cytokines; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases