Influence of shear stress on phenotype and MMP production of smooth muscle cells in a co-culture model

Abstract

BACKGROUND: High shear stress (SS) could affect vascular remodeling during initiation of cerebral aneurysms. However, the response of smooth muscle cells (SMCs) to high SS, which is related to blood vessel remodeling, are poorly understood. OBJECTIVE: We explored the effect of high SS on SMCs in an EC-SMC coculture model to investigate blood vessel remodeling during aneurysm formation. METHODS: SMCs were three-dimensionally cultured in a collagen gel, with ECs cultured on a membrane filter above the SMCs. Then, the co-culture model was exposed to different SS of 0.2, 2, 6, and 10 Pa for 72 h. RESULTS: A physiological SS of 2 Pa maintained the expression of contractile proteins in SMCs, whereas lower or higher SS decreased the expression, suggesting a phenotypic change to a synthetic state. Furthermore, we found that a high SS of 10 Pa increased production of both matrix metalloproteinase (MMP) -2 and -9 from SMCs, which could induce destructive blood vessel remolding. CONCLUSIONS: High SS could change the SMC phenotype to a synthetic state and induce higher MMP production by SMCs in the co-culture model. These results may help to further elucidate blood vessel remodeling mechanisms under high SS conditions.