Overexpression of angiotensin-converting enzyme 2 inhibits angiotensin Ⅱ type 1 receptor expression and signal transducer and activator of transcription 3 phosphorylation in cultured smooth muscle cells
10.3760/cma.j.issn.0253-3758.2012.07.014
- VernacularTitle:血管紧张素转换酶2基因转染抑制大鼠平滑肌细胞血管紧张素Ⅱ1型受体表达及下游转录激活子3信号通路
- Author:
Jing-Jing GONG
1
;
Zhuo-Qiang LU
;
Jin-Long CAO
;
Chang-Sheng XU
;
Hua-Jun WANG
;
Xue-Qing JIN
Author Information
1. 福建医科大学附属第一医院
- Keywords:
Myocytes,smooth muscle;
Peptidyl-dipeptidase A;
Receptor,angiotensin,type 1;
STAT3 transcription factor
- From:
Chinese Journal of Cardiology
2012;40(7):607-613
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of recombinated lentiviral angiotensin-converting enzyme 2 ( ACE2 ) vector transfer on the expression of angiotnsin Ⅱ type 1 ( AT1 ) receptor in cultured vascular smooth muscle cells (VSMCs).Methods VSMCs were divided into 7 groups:( 1 ) Control:serumfree culture medium; (2) Lentiviral-GFP vector group:Lentiviral-GFP vector ( MOI =10) ; ( 3 ) Ang Ⅱ group ( 10-7 mol/L) ;(4)Ang Ⅱ ( 10-7 mol/L) + Lentiviral-ACE2 ( MOI =10) group; (5)Ang Ⅱ ( 10-7 mol/L) +Irbesartan (10-7 mol/L) group ; (6) Ang Ⅱ ( 10-7 mol/L) + irbesartan (10-7 mol/L) + Lentiviral-ACE2 ( MOI =10) group ; ( 7 ) Lentiviral-ACE2 ( MOI =10 ) group.Ninety-six hours later,the proliferation of VSMCs was determined with CCK-8 Kit.AT1 receptor mRNA and protein expressions were detected with quantitative real-time PCR and Western blot,the signaling pathway of signal transducer and activator of transcription 3 (STAT3) was also detected.Results ACE2 gene transfer significantly inhibited the VSMCs proliferation in the absence or presence of Ang Ⅱ.AT1 receptor mRNA and protein expressions were also significantly downregulated in the absence or presence of Ang Ⅱ.Similar to AT1 receptor mRNA and protein expression changes, STAT3 phosphorylation was also significantly inhibited by ACE2 overexpression.Conclusion Our results suggest that overexpression of ACE2 gene could inhibit the VSMCs proliferation by downregulating AT1 receptor expression and STAT3 phosphorylation. ACE2 could also directly inhibit AT1 receptor in cultured VSMCs.
