Abstract: Objective To evaluate the effect of high-salt intake and family history of hypertension on the gene expression of transforming growth factor beta-1（TGF-β1）/Smads and calcium-regulation proteins in human umbilical artery smooth muscle cells（hUASMC）. Methods A lot of fourteen normal fetus were derived into positive hypertension family history group（FH+,n=7）and negative hypertension family history group（FH-,n=7）,and their umbilical cords were collected. HUASMC isolated by tissue explants adherent method were cultured with normal medium（139mmol/L sodium chloride）or high salt medium（164mmol/L sodium chloride）. Smooth muscle cell-specificα-actin was observed through the immunocytochemical method. The real-time reverse transcription polymerase chain reaction was employed to detect the gene expressions of TGF-β1,Smad2,Smad3 and Smad7,Na+-K+-ATPaseα1-subunit,α2-subunit andα3-subunit,plasma membrane Ca2+-ATPase isoform（PMCA）1and PMCA4,as well as transient receptor potential canonical channel（TRPC）1,TRPC3 and TRPC6. Factor analysis method was used to evaluate the interactions of family history of hypertension and high salt on above gene expressions. Results There was no interaction between hypertension family history and high-salt intake on the mRNA expressions of TGF-β1/Smads,α3-subunit,PMCA4,TRPC1 and TRPC6（P＜0.05）,main effects analysis showed that family history of hypertension could promote the expressions of TGF-β1,α3-subunit and TRPC6（P＜0.05）,and inhibit Smad7（P＜0.05）,while high salt intake could promote Smad3 and TRPC1（P＜0.05）,and inhibit PMCA4 and Smad7. There was interaction between hypertension family history and high salt intake on the expressions ofα1-subunit,α2-subunit,PMCA1 and TRPC3（P＜0.05）. When the family history is positive,compared with the control group,the high salt group had increased expression of TRPC3（P＜0.05）,and decreased expressions ofα1-subunit,α2-subunit and PMCA1（P＜0.05）. When the family history is negative,high salt intake could increase the expression of TRPC3（P＜0.05）,but had no effect onα1-subunit,α2-subunit and PMCA1（P＞0.05）. In FH+group,the expressions ofα1-subunit and TRPC3increased（P＜0.05）,with PMCA1decreased（P＜0.05）in high salt condition,while in normal salt condition,the expressions ofα1-subunit,α2-subunit and PMCA1increased（P＜0.05）,with no significant change in TRPC3expression（P＞0.05）. Conclusions Family history of hypertension may affect the mRNA expressions ofα3-subunit and TRPC6,while high salt intake may affect the mRNA expressions of PMCA4 and TRPC1. Hypertension family history and high salt intake may co-regulate the mRNA expressions of TGF-β1/Smads,α1-subunit,α2-subunit,PMCA1 and TRPC3in hUASMC.