Title: Inhibitory Effect of Adenoviral Vector Containing AT_1 Receptor Antisense cDNA on Proliferation of Rat Vascular Smooth Muscle Cells
Abstract: Objective To evaluate the role of human angiotensin Ⅱ (Ang Ⅱ) type 1 receptor (AT 1R)antisense cDNA (ahAT 1) on Ang Ⅱ induced proliferation of cultured rat artery smooth muscle cells (VSMC). Methods Recombinant adenoviral vectors, Ad/CMV·ahAT 1 containing full length of antisense cDNA targeting to human AT 1R mRNA. Another recombinant adenoviral vector Ad/CMV·LacZ containing LacZ(report gene) served as control. Both of them were constructed by orientation clone technique and homologous recombination and were transfected into VSMCs from Wistar rats in vitro. After stimulation by Ang Ⅱ 10 -7 mol/L for 24 h, AT 1R expression was detected by RT PCR and immunohistochemical method. DNA synthesis was determined by 3H TdR incorporation and flow cytometry. Nontransfected VSMCs served as control as well. Results 48 hours after Ad/CMV·ahAT 1 transfected into VSMCs, the level of AT 1R mRNA along with the AT 1R protein expression of VSMCS were decreased markedly. Ang Ⅱ significantly increased the DNA synthesis and proliferation index(PI) of VSMCs in a time dependent manner ( P 0 05 and P 0 01 vs These increase in DNA synthesis and PI of VSMCs were clearly inhibited by Ad/CMV·ahAT 1 to the level of the control, while in some cases even lower ( P 0 05 vs control). No difference in these parameters between group Ang Ⅱ Ad/CMV·LacZ and group Ang Ⅱ were found. Conclusion These results indicate that antisense cDNA targeting to human AT 1R transfered in vitro has powerful inhibitory effect on AngⅡ induced proliferation of VSMCs by attenuating AT 1R expression.
Publication Year: 2003
Publication Date: 2003-01-01
Language: en
Type: article
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