Communication between endothelial cells (EC) and smooth muscle cells (SMC) have been shown to be critical for remodelling of the vessel wall in response to biomechanical forces. In vitro experiments suggest that presence of SMC significantly affects the molecular differentiation of co-cultured EC upon exposure to cyclic stretch. For instance, short-term stimulation with cyclic stretch induces a strong upregulation of monocyte chemoattractant protein 1 (MCP-1) in human umbilical venous EC (HUVEC) which were allowed to interact with human thymus SMC (HTSMC) via paracrine communication. To study the impact of biomechanical forces on the phenotype of vascular cells in a more adequate physiological microenvironment we established an in situ perfusion model employing isolated mouse arteries. Long-term exposure to supraphysiological levels of pressure resulted in significant upregulation of MCP-1 in perfused mouse arteries. Immunhistochemistry analyses of those vessels revealed that the integrity of the endothelial cells is not affected by pressure stimulation as evidenced by CD31 and desmin staining. Comparing the results from isolated endothelial cells and EC co-cultured with SMC, the data identify EC-SMC interaction as a prerequisite for adequate analyses of biomechanically induced differentiation processes of vascular cells.