The aim of the present study was to examine the effect of 1,25(OH)2D3 (calcitriol) on SMC (smooth muscle cell) migration, especially in the context to atherogenesis. SMCs were obtained from the aortas of newborn Wistar rats by enzymatic digestion. Different aspects of cell behavior during migration in culture were examined by phase contrast, fluorescence and electron microscopy (TEM, SEM) and supported by flow cytometric and biochemical analyses. Morphological studies revealed that supra-physiological (1-100 nmol/l) concentrations of calcitriol inhibit SMC differentiation, therefore these cells display several hallmarks of the synthetic state. Dynamic changes in actin cytoskeleton organization were a critical event in SMC shape, adhesion and spreading. Calcitriol diminished stress fibers assembly and focal adhesions formation. Reduced expression of beta1-integrin receptors on SMC surface after exposition to calcitriol coincided with increased proliferative and migratory activities of these cells. Moreover, after calcitriol stimulation, the ability of SMCs to the production of proinflamatory cytokines IFN-gamma, TNF-alpha and IL-6 was inhibited. The results from these comparative investigations indicate that 1,25(OH)2D3 inhibit differentiation and facilitate SMC migration in culture. It has been also suggested that such responses of SMCs to calcitriol play a beneficial role in fibrous cap formation during atherosclerotic process.
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