Loss of lysophospholipase 3 increases atherosclerosis in apolipoprotein E-deficient mice |
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Authors: | Taniyama Yoshio Fuse Hiromitsu Satomi Tomoko Tozawa Ryuichi Yasuhara Yoshitaka Shimakawa Kozo Shibata Sachio Hattori Masahiko Nakata Mitsugu Taketomi Shigehisa |
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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 |
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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. |
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Keywords: | Acylceramide synthase Atherosclerosis Apoptosis Knockout mice LLPL Oxidized LDL Lysophospholipase 3 Lysosomal phospholipase A2 Macrophage |
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