• Leanne E Felkin, Emma J Birks, Robert George, Sissie Wong, Asghar Khaghani, Magdi H Yacoub, and Paul J R Barton.
• National Heart and Lung Institute, Imperial College London, Heart Science Centre, Harefield, Middlesex.
• J. Heart Lung Transplant. 2006 Dec 1;25(12):1413-9.

BackgroundMechanisms underlying the rapid deterioration of heart failure patients who subsequently require left ventricular assist device (LVAD) support are poorly understood. Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play a key role in myocardial remodelling and heart failure. We hypothesized that MMP and TIMP expression would be altered in these patients.MethodsQuantitative polymerase chain reaction was used to measure myocardial messenger RNA levels of MMP1 to MMP14, TIMP1 to TIMP4, collagen I and collagen III in 24 dilated cardiomyopathy (DCM) patients with deteriorating clinical status who required LVAD support (LVAD Group) and in 7 stable DCM patients undergoing transplantation without need for LVAD support (Tx Group).ResultsLevels of MMP1, MMP8 and TIMP4 were higher in the LVAD Group compared with the Tx Group (188% +/- 141%, 646% +/- 432%, and 66% +/- 33% higher, respectively, p < 0.05) whereas MMP2, MMP9, MMP10, MMP11, and MMP14 levels were similar. MMP3, MMP7, MMP12, and MMP13 were undetectable. All TIMPs were generally higher in the LVAD group, but only TIMP4 reached significance. Collagen I and III were not altered. We tested for correlations between MMP and TIMP expression with myocardial cytokine levels. MMP8 correlated positively with interleukin-6 and interleukin-1beta, suggesting a link between cytokines and MMPs in these patients.ConclusionsThe data show that high myocardial collagenase (MMP1 and MMP8) expression without compensatory changes in collagen or TIMP expression is a feature of patients requiring LVAD support. This may be linked in part to elevated cytokine expression and suggests collagenase activity may be an important therapeutic target in deteriorating heart failure.

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