Inhibitory effects of antisense β1 integrin oligodeoxynucleotides on DNA synthesis in cardiac fibroblasts induced by arginine vasopressin

AIM: To explore the effects of β1 integrin antisense oligodeoxynucleotides (ASODN) on the DNA synthesis in cardiac fibroblasts (CFs) induced by arginine vasopressin (AVP). METHODS: CFs of Sprague Dawley neonatal rats were separated and cultured using trypsin. MTT techniques and enzyme-linked immunosorbent assay (ELISA) were adopted to evaluate the number and expression of β1 integrin in CFs. DNA synthesis was measured by incorporation of 3H-thymidine (3H-TdR) in blank control group (n=8), β1 integrin sense oligodeoxynucleotide group (n=8) and β1 integrin ASODN group (n=8). The effects of β1 integrin ASODN on the DNA synthesis in CFs pretreated with AVP were also observed. RESULTS: The number of CFs cultured and the 3H-TdR incorporation value in CFs by ASODN were significantly lower than in control and sense group (P<0.01). In the group pretreated with 1×10-7 mol/L AVP and group of sense+1×10-7 mol/L AVP, the expression of β1 integrin in CFs and the number of CFs were significantly higher than in control (P<0.05), whereas in the group of added ASODN+1×10-7 mol/L AVP, the expression of 1 integrin and the number of CFs was significantly lower than in 1×10-7 mol/L AVP group and sense oligos+1×10-7 mol/L AVP group (P<0.01). In the group pretreated with 1×10-7 mol/L AVP and group of sense+1×10-7 mol/L AVP, the 3H-TdR incorporation value in CFs was significantly higher than in control (P<0.05), whereas the 3H-TdR incorporation value in CFs with added ASODN+1×10-7 mol/L AVP was significantly lower than in blank control group, 1×10-7 mol/L AVP group and sense oligos+1×10-7 mol/L AVP group (P<0.01). CONCLUSION: CF proliferation and DNA synthesis can be effectively inhibited by β1 integrin ASODN. The effects of AVP on the expression of β1 integrin in CFs, CF proliferation and DNA synthesis can also be effectively inhibited by ASODN, but they are not weakened by sense oligodeoxynucleotides, indicating that restraining of a gene segment would limit one of the steps of information transduction on expression of integrin, inhibit the transduction of cell information, interfere with the inhesion of ECM and CFs, and then reverse cardiac remodeling by AVP. β1 integrin ASODN may be a new drug for modulating interstitial remodeling in essential hypertensive patients.