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Int J Clin Exp Pathol 2012;5(7):698-706

Original Article
Effect of GPE-AGT nanoparticle shRNA transfection system mediated RNAi on early
atherosclerotic lesion

Ping Lu, Lifen Yuan, Yuqiang Wang, Qin Du, Jing Sheng

Department of Geriatrics, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, No 639 Zhizaoju Road, Shanghai, 200011,
China

Received June 30, 2012; Accepted August 2, 2012; Epub September 5, 2012; Published September 15, 2012

Abstract: Objective: To investigate the effects of RNA interference targeting AGT on early atherosclerotic lesion in the hypertensive state.
Methods: Hypertension and atherosclerosis rats were treated with GPE nanoparticles carrying AGT shRNA. Systolic blood pressure and heart
rate were measured for 2 consecutive weeks. Three days after treatment, the mRNA and protein expressions of AGT in the liver were measured
by PCR and western blot assay, respectively. The blood levels of AGT and Ang II were determined by ELISA. H&E staining and electron
microscopy were performed. Results: Three days after AGT shRNA treatment, the mRNA and protein expressions of AGT in the liver were
markedly reduced and the blood levels of AGT and Ang II dramatically decreased as compared to the remaining 3 groups (P < 0.05). Three
days after AGT shRNA treatment, the blood pressure was reduced by 27 ± 4mmHg when compared with that at baseline (P < 0.05). About 11
days after AGT shRNA treatment, the blood pressure began to increase. The blood pressure remained unchanged in the remaining 3 groups.
Microscopy showed the atherosclerotic lesions were markedly attenuated in AGT shRNA treated rats but the liver and kidney functions
remained stable (P > 0.05) when compared with the remaining 3 groups. Conclusion: Transfection with GPE nanoparticle carrying AGT shRNA
can stably lower the blood pressure and improve the atherosclerotic lesions which lead to the delayed development of early atherosclerotic
lesions in hypertension rats with concomitant atherosclerosis. (IJCEP1206012).

Keywords: Angiotensinogen, RNA interference, hypertension, atherosclerosis, spontaneously hypertensive rat, animal model

Address all correspondence to:
Dr. Jing Sheng,
Department of Geriatrics, Ninth People’s Hospital,
Shanghai Jiaotong University School of Medicine, No
639 Zhizaoju Road, Shanghai, 200011, China;
Email: shengjing60@163.com