Effects of RNA interference targeting angiotensin-converting enzyme on the blood pressure and myocardial remodeling in spontaneously hypertensive rats
10.3321/j.issn:0253-3758.2008.03.015
- VernacularTitle:RNA干扰血管紧张素转换酶对自发性高血压大鼠血压及心肌重构的影响
- Author:
Jun-Hua HE
1
;
Chuan-Shi XIAO
;
Mao-Lian LI
;
Yun-Fei BIAN
Author Information
1. 山西医科大学第二医院
- Keywords:
Hypertension;
Peptidyl-dipeptidase A;
RNA interference: Rats
- From:
Chinese Journal of Cardiology
2008;36(3):249-253
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of RNA interference(RNAi)targeting angiotensinconverting enzynle(ACE)on the blood pressure and myocardial remodeling in spontaneously hypertensive rats(SHRs).Methods Saline(control),adenovirus(Ad5)and recombinant adenoviral vectors(Ad5-ACE-shRNA expressing ACE gene-specific shRN)were randomly administered by caudal intravenation to SHRs(n=12 each group)at day 1 and day 16.Normotensive Wistar-Kyoto rats(WKY)served as normal controls.Systolic blood pressure(SBP)of the caudal artery was measured daily.Expressions of ACE at mRNA and protein levels in myocardium and aorta were evaluated by RT-PCR and Western blot respectively,ACE serum concentration was measured by ELISA at day 3(n=6 each group).The ratio of left ventricular to body weight(LVW/BW),myocardial collagen content were measured and myocardial uhrastrueture observed under transmission electron microscope at the study end.Results Ad5-ACE-shRNA injection significantly reduced SBP(-22 mm Hg,1 mm Hg=0.133 kPa)and the antihypertensive effect could last at least 14 davs post each injection.SBP was not affected by saline and Ad5 injections.ACE expressions at mRNA and Drotein levels at myocardium and aorta as well as serum ACE were significantly decreased in Ad5-ACE-shRNA treated SHRs compared to that in saline and Ad5 groups(all P＜0.05)and was coinparable to that in WKY group(P＞0.05).The LVW/BW ratio(2.24±0.19)and myocardial collagen content[(1.283±0.019)μg/mg]in Ad5-ACE-shRNA treated SHRs were also significantly lower than those in saline treated[3.21±0.13 and (1.686±0.013)μg/mg,both P＜0.05]and Ad5 treated SHRs [3.13 ±0.12,(1.682±0.009)μg/mg,both P＜0.05]but still higher than those of WKY group[2.06±0.11,(1.257±0.019)μg/mg,both P＜0.05].Myocardial uhrastructure was also significantly improved in Ad5-ACE-shRNA treated SHRs compared to saline and Ad5 treated SHRs.Conclusion RNAi targeting ACE gene significantly inhibited the expressions of ACE at mRNA and protein levels and resuhed in prolonged antihypertensive effects and myocardial uhrastructure improvements in this SHR model.
