AIMS: 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. METHODS AND 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.
AIMS: 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. METHODS AND 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: F G Spinale; M L Coker; S R Krombach; R Mukherjee; H Hallak; W V Houck; M J Clair; S B Kribbs; L L Johnson; J T Peterson; M R Zile Journal: Circ Res Date: 1999-08-20 Impact factor: 17.367
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Authors: J H McElmurray; R Mukherjee; R B New; A C Sampson; M K King; J W Hendrick; A Goldberg; T J Peterson; H Hallak; M R Zile; F G Spinale Journal: J Pharmacol Exp Ther Date: 1999-11 Impact factor: 4.030
Authors: Zamaneh Kassiri; Gavin Y Oudit; Otto Sanchez; Fayez Dawood; Fazilat F Mohammed; Robert K Nuttall; Dylan R Edwards; Peter P Liu; Peter H Backx; Rama Khokha Journal: Circ Res Date: 2005-07-21 Impact factor: 17.367
Authors: Hao Chen; Donghang Zheng; Jeff Abbott; Liying Liu; Mee Y Bartee; Maureen Long; Jennifer Davids; Jennifer Williams; Heinz Feldmann; James Strong; Katrina R Grau; Scott Tibbetts; Colin Macaulay; Grant McFadden; Robert Thoburn; David A Lomas; Francis G Spinale; Herbert W Virgin; Alexandra Lucas Journal: Antimicrob Agents Chemother Date: 2013-06-17 Impact factor: 5.191
Authors: Vishnu Chintalgattu; Joanne Greenberg; Shivani Singh; Venice Chiueh; Amy Gilbert; Jason W O'Neill; Stephen Smith; Simon Jackson; Aarif Y Khakoo; TaeWeon Lee Journal: Pharmacol Res Perspect Date: 2018-11-14