Loss of lysophospholipase 3 increases atherosclerosis in apolipoprotein E-deficient mice

Taniyama, Yoshio; Fuse, Hiromitsu; Satomi, Tomoko; Tozawa, Ryuichi; Yasuhara, Yoshitaka; Shimakawa, Kozo; Shibata, Sachio; Hattori, Motonobu; Nakata, Mitsugu; Taketomi, Shigehisa

doi:10.1016/j.bbrc.2005.02.126

Cited by 17 publications

(11 citation statements)

References 18 publications

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“…Protective effect of normal activity thought due to acylation of ceramide. Macrophages from LYPLA3 KO mice were more prone to apoptosis upon exposure to oxLDL (1758).…”

Section: Lypla3 (Pla2g15) Lypla3mentioning

confidence: 92%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

382

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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“…Protective effect of normal activity thought due to acylation of ceramide. Macrophages from LYPLA3 KO mice were more prone to apoptosis upon exposure to oxLDL (1758).…”

Section: Lypla3 (Pla2g15) Lypla3mentioning

confidence: 92%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

382

344

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“…511 LPLA 2 and apoE double knockout mice showed increased lesion formation but little effect on the plasma-lipid profile when fed on a normal diet. However the double knockout mice did not show a significant difference in the extent of atherogenesis when fed an atherogenic, Western-style diet.…”

Section: Lysosomal Phospholipase A2 [Group XV Lpla2]mentioning

confidence: 94%

“…However the double knockout mice did not show a significant difference in the extent of atherogenesis when fed an atherogenic, Western-style diet. 511 Thioglycolate-elicited peritoneal macrophages from the double knockout mice were more sensitive to apoptosis induced by oxLDL. 511 All together, this suggests that LPLA 2 may play an important role in atherogenesis.…”

Section: Lysosomal Phospholipase A2 [Group XV Lpla2]mentioning

confidence: 97%

Phospholipase A₂ Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

et al. 2011

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“…These data suggest that LPLA 2 may have a role in long term immunoregulation. Taniyama and coworkers also described an LPLA 2 knockout mouse (21). These mice, when bred on an apoE null background and fed a high fat diet, displayed an increase in the area of the aortic tree associated with atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

The Secretion and Uptake of Lysosomal Phospholipase A2 by Alveolar Macrophages

Abe

Kelly

Kollmeyer

et al. 2008

The Journal of Immunology

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Macrophages have long been known to secrete a Phospholipase A2 with an acidic pH optimum in response to phagocytic stimuli. However, the enzyme or enzymes responsible for this activity have not been identified. We report that mouse alveolar macrophages release lysosomal phospholipase A2 (LPLA2) into the medium of cultured cells following stimulation with zymosan. The release of the enzyme was detected by enzymatic activity assays as well as by Western blotting using an Ab against mouse LPLA2. LPLA2 is a high mannose type glycoprotein found in lysosomes, suggesting that the released enzyme might be reincorporated into alveolar macrophages via a mannose or mannose phosphate receptor. Recombinant glycosylated mouse LPLA2 produced by HEK293 cells was applied to LPLA2-deficient (LPLA2−/−) mouse alveolar macrophages. The uptake of exogenous LPLA2 into LPLA2−/− alveolar macrophages occurred in a concentration-dependent manner. The LPLA2 taken into the alveolar macrophages colocalized with the lysosomal marker, Lamp-1. This uptake was significantly suppressed in the presence of α-methyl-mannoside but not in the presence of mannose 6-phosphate. Thus, the predominant pathway for uptake of exogenous LPLA2 is via the mannose receptor, with subsequent translocation into acidic, Lamp-1-associated compartments. LPLA2−/− alveolar macrophages are characterized by marked accumulation of phosphatidylcholine and phosphatidylethanolamine. Treatment with the recombinant LPLA2 rescued the LPLA2−/− alveolar macrophages by markedly decreasing the phospholipid accumulation. The application of a catalytically inactive LPLA2 revealed that the enzymatic activity of LPLA2 was required for the phospholipid reduction. These studies identify LPLA2 as a high m.w.-secreted Phospholipase A2.

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Loss of lysophospholipase 3 increases atherosclerosis in apolipoprotein E-deficient mice

Cited by 17 publications

References 18 publications

Molecular Biology of Atherosclerosis

Molecular Biology of Atherosclerosis

Phospholipase A₂ Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

The Secretion and Uptake of Lysosomal Phospholipase A2 by Alveolar Macrophages

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Loss of lysophospholipase 3 increases atherosclerosis in apolipoprotein E-deficient mice

Cited by 17 publications

References 18 publications

Molecular Biology of Atherosclerosis

Molecular Biology of Atherosclerosis

Phospholipase A2 Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

The Secretion and Uptake of Lysosomal Phospholipase A2 by Alveolar Macrophages

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Product

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Phospholipase A₂ Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention