title: Loss of lysophospholipase 3 increases atherosclerosis in apolipoprotein E-deficient mice.
abstract: Human LCAT-like lysophospholipase (LLPL), or lysophospholipase 3, was first identified in vitro, in foam cells derived from THP-1 cells. We demonstrated that LLPL was present in foam cells in the severe atherosclerotic lesions that develop in apolipoprotein E-null (apoE(-/-)) mice. This indicated that LLPL might affect lipid metabolisms in foam cells and, therefore, atherogenesis. Accordingly, we created LLPL-knockout mice by gene targeting and crossed them with apoE(-/-) mice. We showed that the absence of LLPL increased lesion formation markedly in apoE(-/-) mice but had little effect on the plasma-lipid profile. In addition, LLPL-deficient peritoneal macrophages were more sensitive to apoptosis induced by exposure to oxidized low-density lipoprotein. LLPL might provide a link between apoptosis in macrophages and atherogenesis. Our data demonstrate that LLPL activity is anti-atherogenic and indicate that the regulation of this enzyme might be a novel drug target for the treatment of atherosclerosis.
authors.affiliation: Biomedical Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 17-85, Jusohonmachi 2-chome, Yodogawa-ku, Osaka 532-8686, Japan. Taniyama_Yoshio@takeda.co.jp <Taniyama_Yoshio@takeda.co.jp>
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Taniyama
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Fuse
authors.forename: Tomoko
authors.initials: T
authors.lastname: Satomi
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Tozawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yasuhara
authors.forename: Kozo
authors.initials: K
authors.lastname: Shimakawa
authors.forename: Sachio
authors.initials: S
authors.lastname: Shibata
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hattori
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Nakata
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Taketomi
mesh_terms: D000215:Acylation; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis; D001161:Arteriosclerosis / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008245:Lysophospholipase / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D008245:Lysophospholipase