HIV-infected individuals are at increased risk of cardiovascular events, possibly owing to accelerated atherosclerosis. The mechanisms involved are unclear. The chemokine receptor CCR5 is a major co-receptor for the HIV virus. Interestingly, CCR5 deficiency results in a reduction in diet-induced atherosclerosis in mice (Braunersreuther et al., 2007) and CCR5 and its ligand MIP1-β are expressed in human vascular smooth muscle (Schecter et al., 2000). A direct effect on vascular tone of chemokines has not been reported. Human saphenous vein (SV) is a widely used graft in patients with coronary artery disease however, grafts, particularly SV, exhibit a form of accelerated atherosclerosis making this blood vessel a useful model of disease. In initial experiments we have determined whether MIP1-β has direct constrictor/dilator action in SV and confirmed that this is a CCR5 mediated action using the selective antagonist maraviroc (UK-427,857; Dorr et al., 2005). Rings (4mm) of human SV were denuded of their endothelium and mounted in organ baths, containing Krebs’ solution at 37°C, for isometric tension recording. Following a normalisation procedure to optimise basal tension, endothelium removal was confirmed by the absence of a vasodilator response to ACh in phenylephrine constricted veins. Cumulative concentration-response curves (CRC) were then constructed to MIP1-β (10^-11-1.1×10^-7M). In adjacent rings of SV from some patients, 300nM maraviroc or vehicle (DMSO 0.01%) were added to the bathing medium and cumulative CRC to MIP1-β constructed 30 minutes later. In additional experiments, CRC to MIP1-β were constructed in SV that had been preconstricted with endothelin-1 (10nM) and experiments terminated by addition of 30μM SNAP. Vasoconstrictor responses were expressed as a %phenylephrine and vasodilator responses as %reversal of ET-1 constriction. Data were analysed using FigSys (Biosoft, Cambridge, UK) to determine values of pD₂ and maximum response. n-Values are the number of patients from whom tissue was obtained. In ET-1 constricted SV, MIP1-β did not elicit direct vascular smooth muscle relaxation over the concentration range tested. In contrast MIP1-β produced a concentration-dependent contraction of SV with pD₂ of 7.73±0.17 (n=12). In the presence of 300nM maraviroc (n=4), the constrictor response to MIP1-β was abolished (Fig 1). These data reveal a previously unidentified role for the chemokine MIP1-β as a potent constrictor of human SV, an effect mediated through the CCR5 receptor present on vascular smooth muscle.