title: Lentivirus-mediated RNA interference of chymase increases the plaque stability in atherosclerosis in vivo.
abstract: Chymase activity was proved to be closely related with plaque vulnerability in a hamster model of atherosclerosis with chymase inhibitors. Considering that chymase inhibitors are nonspecific, here we further investigated the role of chymase in atherosclerosis in vivo through injection of lentivirus containing chymase shRNA or chymase cDNA. Our results revealed that silencing of the chymase gene by shRNA remarkably enhanced atherosclerosis plaque stability without alterations in body weight or serum lipid levels. Lentiviral expression of a gain-of-function chymase gene promoted the formation of vulnerable plaque in hamsters. Mechanistically, chymase functions as an activator of MMP9 in atherosclerotic lesions that induces plaque instability.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan City, Shandong 250012, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Jianmin
authors.initials: J
authors.lastname: Yang
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Chen
authors.forename: Guipeng
authors.initials: G
authors.lastname: An
authors.forename: Lu
authors.initials: L
authors.lastname: Fan
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Peng
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology*; D053818:Chymases / Q000235:genetics* / Q000378:metabolism; D006224:Cricetinae; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D016086:Lentivirus / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000201:enzymology* / Q000473:pathology / Q000821:virology; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D008055:Lipids; D034741:RNA, Small Interfering; D053818:Chymases; D020780:Matrix Metalloproteinase 9
keywords: Atherosclerosis; Chymase; Matrix metalloproteinase 9; RNA interference