title: Effect of GPE-AGT nanoparticle shRNA transfection system mediated RNAi on early atherosclerotic lesion.
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 ± 4 mmHg 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Geriatrics, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Lifen
authors.initials: L
authors.lastname: Yuan
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Qin
authors.initials: Q
authors.lastname: Du
authors.forename: Jing
authors.initials: J
authors.lastname: Sheng
mesh_terms: D000809:Angiotensins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001794:Blood Pressure / Q000235:genetics; D002339:Carotid Arteries / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006339:Heart Rate / Q000235:genetics; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D011918:Rats, Inbred SHR; D014162:Transfection
chemical_list: D000809:Angiotensins; D012333:RNA, Messenger; D034741:RNA, Small Interfering