RNA interference targeting the ACE gene reduced blood pressure and improved myocardial remodelling in SHRs

Autor: Ling Qiu, Gaizhen Liu, Chuanshi Xiao, Hua Zhou, Jun-Hua He, Fen Gao, Weidong Wu, Yun-fei Bian, Mao-lian Li
Rok vydání: 2009
Předmět:
Zdroj: Clinical Science. 116:249-255
ISSN: 1470-8736
0143-5221
DOI: 10.1042/cs20080048
Popis: The purpose of the present study was to investigate the effects on blood pressure and myocardial hypertrophy in SHRs (spontaneously hypertensive rats) of RNAi (RNA interference) targeting ACE (angiotensin-converting enzyme). SHRs were treated with normal saline as vehicle controls, with Ad5-EGFP as vector controls, and with recombinant adenoviral vectors Ad5-EGFP-ACE-shRNA, carrying shRNA (small hairpin RNA) for ACE as ACE-RNAi. WKY (Wistar–Kyoto) rats were used as normotensive controls treated with normal saline. The systolic blood pressure of the caudal artery was recorded. Serum levels of ACE and AngII (angiotensin II) were determined using ELISA. ACE mRNA and protein levels were determined in aorta, myocardium, kidney and lung. On day 32 of the experiment, the heart was pathologically examined. The ratios of heart weight/body weight and left ventricular weight/body weight were calculated. The serum concentration of ACE was lower in ACE-RNAi rats (16.37±3.90 ng/ml) compared with vehicle controls and vector controls (48.26±1.50 ng/ml and 46.67±2.82 ng/ml respectively; both P0.05). The serum concentration of AngII was also significantly lower in ACE-RNAi rats (18.24±3.69 pg/ml) compared with vehicle controls and vector controls (46.21±5.06 pg/ml and 44.93±4.12 pg/ml respectively; both P0.05). The expression of ACE mRNA and ACE protein were significantly reduced in the myocardium, aorta, kidney and lung in ACE-RNAi rats compared with that in vehicle controls and in vector controls (all P
Databáze: OpenAIRE