Heart failure is characterised by an increase in circulating catecholamine levels and alterations to the cardiac extracellular matrix (ECM) – the latter of which we have found to be strongly influenced by age (1). Despite this association little is known regarding how β-adrenergic signalling modulates cardiac fibroblast (CF) – dependent remodelling of the ECM. The aims of this study were; i) determine if β-adrenergic stimulation of CFs alters production of matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) and, ii) determine whether these secreted levels change with age. Female Welsh Mountain ewes aged either 18 months (young) or >8 years (aged) were killed by intravenous administration of 200 mg.kg-1 pentobarbitone sodium following 10,000 U of heparin. CFs were isolated from LV samples (~0.5g) by incubation with 1,000 U/ml collagenase type II (Worthington) for 90mins. Primary cultures were maintained at 37oC, 5% CO2. CF proliferation was measured at passage 3 using a CyQUANT Direct Cell Proliferation Assay kit (Life Technologies). Confirmation that isolated cells were CFs and that they expressed the β2-adrenoreceptor (β2-AR) was carried out by immunostaining. At passage 4, 2x10e6 cells were seeded in 225cm2 culture flasks, serum-starved for 24h, and then media replaced with that containing either PBS (control), 0.1, 1 or 10μM isoprenaline (ISO) for 48h. After which, conditioned-media was collected, concentrated with centrifugal filters (Millipore) and assessed for MMP activity (gelatin zymography) and TIMP proteins (immunoblotting). In these experiments, each sample was run in triplicate and data expressed as a mean change ± standard error of the mean and normalised to vimentin protein level in cell pellet extracts. All statistical comparisons were made using a 2-way repeated measures analysis of variance, apart from the proliferation assay where a t-test was performed. All cells isolated were positive for the fibroblast marker vimentin. CFs also expressed the β2AR. Proliferation was increased in aged CFs compared to young (P<0.05, n=9 young & 6 aged). Overall, MMP-2 activity in the CF conditioned media was less after treatment with 1μM compared to 0.1μM ISO (P<0.01, n=4 young & 4 aged). Although TIMP-1 protein levels were unchanged with either ISO or ageing, TIMP-2 protein was diminished after treatment with both 1 and 10μM ISO in both the young and the aged CFs (all P<0.01, n=4 young & 4 aged). These initial experiments suggest that β-adrenergic signalling may play a role in ECM remodelling by altering levels of key players in matrix remodelling, but ageing has little effect on these changes. All procedures accord to The UK Animals (Scientific Procedures) Act, 1986.