Objective To explore the dose-time-dependent relationship of shear stress and different exposure times on the expression of THBS4 in HASMCs, and to reveal its potential mechanism in vascular remodeling, with the aim of guiding the treatment of clinical cardiovascular diseases. Methods HASMCs were subjected to shear stress of 0, 4, 8 and 12 dyn / cm2 using a parallel plate flow chamber for 6 and 12 h, respectively, and the cells were collected after treatment. mRNA expression of THBS4 was detected by real-time fluorescence quantitative polymerase chain reaction and protein expression was detected by Western blot. The co-localization of THBS4 and cleaved-Caspase8 was examined by immunofluorescence staining. Results The mRNA and protein expression levels of THBS4 gradually increased with increasing shear stress and exposure duration ( P< 0. 05). THBS4 gene and protein levels were significantly higher in shear-H group than in control, shear-L and shear-M groups(P<0. 05). Immunofluorescence detection demonstrated that THBS4 was co-localized with cleaved-Caspase8 and exhibited consistent expression levels. Conclusions Spatiotemporal gradient changes in shear stress can regulate the expression of THBS4 in HASMCs, and its expression level is positively correlated with the magnitude of shear stress, with a time-dependent cumulative effect. These result suggest that THBS4 may modulate apoptotic pathways in HASMCs under shear stress.