title: Hypolipidemic effect of SR‑BI gene delivery by combining cationic liposomal microbubbles and ultrasound in hypercholesterolemic rats.
abstract: High-density lipoprotein (HDL) is a key mediator in reverse cholesterol transport and is involved in a mechanism known as 'selective lipid uptake', a process mediated by scavenger receptor B type I (SR‑BI), which is a HDL receptor. The aim of the present study was to investigate the therapeutic effect of the SR‑BI gene when delivered by combining cationic liposomal microbubbles (CLMs) and ultrasound (US) in hypercholesterolemic rats. Hypercholesterolemia was induced by administration of excessive doses of vitamin D3 and cholesterol in rats. The CLMs consisted of perfluoropropane gas encapsulated in a phospholipid shell using the sonication‑lyophilization method. The SR‑BI gene, mixed with the self‑made microbubbles, was transfected into hypercholesterolemic rat arteries using therapeutic US. SR‑BI protein expression was determined by western blot analysis 2 days post-transfection. Two weeks after transfection, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and HDL serum concentrations were measured. Transfection efficiency of the SR‑BI gene in the SR‑BI + US/CLM group increased 6‑7‑fold compared with the SR‑BI group. Two weeks after transfection, plasma lipid levels in treated hypercholesterolemic rats were observed to be significantly reduced compared with rats that did not receive treatment. However, no significant change was observed in the SR‑BI group compared with that in the SR‑BI + US/CLM group. Results of the present study indicate that the combination of US and CLMs loaded with the SR‑BI gene may exert a protective role in hypercholesterolemia.
authors.affiliation: Department of Ultrasound, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Jiaan
authors.initials: J
authors.lastname: Zhu
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Mengjie
authors.initials: M
authors.lastname: Rui
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Xu
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002412:Cations / Q000737:chemistry; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000378:metabolism / Q000627:therapeutic use*; D008075:Lipoproteins, HDL / Q000097:blood; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D045423:Microbubbles; D051381:Rats; D017207:Rats, Sprague-Dawley; D051122:Scavenger Receptors, Class B / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D014162:Transfection; D014280:Triglycerides / Q000097:blood; D014465:Ultrasonics; D014463:Ultrasonography
chemical_list: D002412:Cations; D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D008081:Liposomes; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; D002784:Cholesterol