Abstract 4952: Differential Expression in the Determinants of Extracellular Matrix Remodeling in Pediatric and Adult Dilated Cardiomyopathy
Circulation(2008)
摘要
Ventricular phenotype of idiopathic dilated cardiomyopathy (DCM) can appear similar in pediatric and adult patients, but a more aggressive clinical course often occurs with pediatric DCM. 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 tests the hypothesis that different MMP/TIMP profiles occur in pediatric and adult DCM patients. Left ventricular samples were taken from pediatric (age 12±4 yr; n=5) and adult (age 63±3 yr; n=11) patients during heart transplantation for DCM. Myocardial levels were quantified for all MMP classes: gelatinases (MMP-2, -9), collagenases (MMP-8, -13), lysins (MMP-7), membrane-type (MT1-MMP), and for all 4 known TIMPs. Patients with structural or ischemic etiologies of DCM were excluded. Compared to adults, MMP-8 levels increased by over 350% (Figure ), and MMP-7 and MT1-MMP levels (75±9% and 76±9%, respectively; p<0.05) were lower in pediatric patients. In contrast, pediatric TIMP-1 levels were reduced by over 50% (Figure). Pediatric DCM patients manifest a robust increase in MMP-8, which degrades all components of the extracellular matrix, and a decrease in TIMP-1, which inhibits MMP-8. This heightened MMP-8/TIMP-1 ratio would favor aggressive matrix remodeling in pediatric DCM. Since MMP-8 is primarily expressed by macrophage cell lineage, a unique proteolytic program may exist in pediatric DCM. These distinct differences in determinants of myocardial matrix structure and function likely contribute to the more progressive nature of DCM in children.
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关键词
extracellular matrix remodeling,differential expression
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