title: Lentiviral-mediated RNA interference of lipoprotein-associated phospholipase             A2 ameliorates inflammation and atherosclerosis in apolipoprotein E-deficient             mice.
abstract: Lipoprotein associated phospholipase A2 (Lp-PLA2) overexpression is implicated             in athero-sclerosis. In the present study, we evaluated the effects of lentiviral-mediated             RNA interference (RNAi) of Lp-PLA2 on inflammation and atherosclerosis in apolipoprotein E-deficient             mice. Apolipoprotein E-deﬁcient mice were randomly allocated to control and experimental             groups, and constrictive collars were used to induce plaque formation. Eight weeks             after surgery, the lentiviral-mediated RNAi construct was used to silence expression             of Lp-PLA2. Control and experimental lentivirus was transfected directly into             carotid plaques or administered systemically. Tissues were collected for analysis             7 weeks after transfection. Inflammatory gene expression in the plasma and atherosclerotic             lesions was then determined at the mRNA and protein levels. We observed no differences             in body weight and plasma lipid levels at the end of the investigation. However,             the expression levels of Lp-PLA2 and pro-inflammatory cytokines were significantly             reduced in the RNAi groups, compared to the controls, whereas the plasma concentration             of anti-inflammatory cytokines was markedly increased. Moreover, our results demonstrated             a significant reduction in plaque area and lipid content, as well as a rise in             collagen content following RNAi treatment. Importantly, when comparing the two             methods of viral delivery, we found that transluminal local transfection exhibited             enhanced improvement of plaque stability as compared to systemic administration.             Inhibition of Lp-PLA2 by lentiviral-mediated RNAi ameliorates inflammation and             atherosclerosis in apolipoprotein E-deficient mice. In addition, transluminal             local delivery of Lp-PLA2 shRNA is superior to systemic administration for stabilizing             atherosclerotic plaques.
authors: Department of Cardiology, The First Affliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
authors: Hui
authors: H
authors: Zhang
authors: Jinying
authors: J
authors: Zhang
authors: Deliang
authors: D
authors: Shen
authors: Li
authors: L
authors: Zhang
authors: Fei
authors: F
authors: He
authors: Yuhua
authors: Y
authors: Dang
authors: Ling
authors: L
authors: Li
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D001835:Body Weight; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D007249:Inflammation / Q000235:genetics / Q000628:therapy*; D016086:Lentivirus / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D014162:Transfection
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D008055:Lipids; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase