Expression of secretory phospholipase A2s in human atherosclerosis development

Kimura-Matsumoto, M; Ishikawa, Yukio; Komiyama, Kanki; Tsuruta, Tadashi; Murakami, Makoto; Masuda, Shiro; Akasaka, Yoshikiyo; Ito, Kinji; Ishiguro, S; Morita, Hiroshi; Sato, Shinji; Ishii, Toshiharu

doi:10.1016/j.atherosclerosis.2006.08.062

Cited by 64 publications

(59 citation statements)

References 31 publications

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“…6). Consistent with our immunohistochemical results, detection of PLA2G3 mRNA in macrophages and vascular smooth muscle cells of human atherosclerotic lesions by means of in situ hybridization has been described recently (40), indicating that PLA2G3 is synthesized in the aortic walls. These observations raise the possibility that PLA2G3 may also act on lipoproteins within the subendothelium at the atherosclerotic foci.…”

Section: Discussionsupporting

confidence: 92%

“…Reportedly, PLA2G2F shows a ϳ2-fold preference for arachidonic acid over linoleic acid in vitro (63), and its ability to hydrolyze PC is similar to that of PLA2G3 both in vitro and in cultured cells (18). Although the pathophysiological relevance of these observations is still unclear, a recent study has shown the inducible expression of PLA2G2F (in addition to several other sPLA 2 s) in human atherosclerotic plaques (40). Therefore, it will be interesting to examine whether alterations in plasma lipoproteins and in the process of atherosclerosis also take place in mice with Tg expression or gene ablation of this unique group II sPLA 2 enzyme, of which the behavior and function in vivo are scarcely understood.…”

Section: Discussionmentioning

confidence: 95%

“…Rabbit antisera for human and mouse PLA2G2A, PLA2G5, and PLA2G10 have been described previously (15,19). Immunostaining for human ␣-smooth muscle actin (SMA) (clone 1A4; Dako Cytomation) and human macrophages (clone HAM56; Dako Cytomation) was also performed using the EnVisionϩ kit (Dako Cytomation) for identification of smooth muscle cells and monocytes/ macrophages, respectively (40). Double immunostaining with antibodies against ␣-SMA or HAM56 and PLA2G3 was performed on the sections to determine the localization of PLA2G3 in intimal cells.…”

Section: Methodsmentioning

confidence: 99%

“…Atherosclerotic lesions are classified into five categories, namely adaptive intimal thickening and types I, II, III, and IV lesions (40). In this study, we examined the immunohistochemical localization of PLA2G3 in normal aorta (without atherosclerosis and fibrocellular thickening), aorta with fatty streaks (type III lesion), and aorta with atheroma (type IV lesion).…”

Section: Pla2g3-treated Ldl Facilitates Macrophage Foam Cell Formatiomentioning

confidence: 99%

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Analyses of Group III Secreted Phospholipase A2 Transgenic Mice Reveal Potential Participation of This Enzyme in Plasma Lipoprotein Modification, Macrophage Foam Cell Formation, and Atherosclerosis

Sato

Kato²,

Isogai

et al. 2008

Journal of Biological Chemistry

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Among the many mammalian secreted phospholipase A 2 (sPLA 2 ) enzymes, PLA2G3 (group III secreted phospholipase A 2 ) is unique in that it possesses unusual N-and C-terminal domains and in that its central sPLA 2 domain is homologous to bee venom PLA 2 rather than to other mammalian sPLA 2 s. To elucidate the in vivo actions of this atypical sPLA 2 , we generated transgenic (Tg) mice overexpressing human PLA2G3. Despite marked increases in PLA 2 activity and mature 18-kDa PLA2G3 protein in the circulation and tissues, PLA2G3 Tg mice displayed no apparent abnormality up to 9 months of age. However, alterations in plasma lipoproteins were observed in PLA2G3 Tg mice compared with control mice. In vitro incubation of low density (LDL) and high density (HDL) lipoproteins with several sPLA 2 s showed that phosphatidylcholine was efficiently converted to lysophosphatidylcholine by PLA2G3 as well as by PLA2G5 and PLA2G10, to a lesser extent by PLA2G2F, and only minimally by PLA2G2A and PLA2G2E. PLA2G3-modified LDL, like PLA2G5-or PLA2G10-treated LDL, facilitated the formation of foam cells from macrophages ex vivo. Accumulation of PLA2G3 was detected in the atherosclerotic lesions of humans and apoE-deficient mice. Furthermore, following an atherogenic diet, aortic atherosclerotic lesions were more severe in PLA2G3 Tg mice than in control mice on the apoE-null background, in combination with elevated plasma lysophosphatidylcholine and thromboxane A 2 levels. These results collectively suggest a potential functional link between PLA2G3 and atherosclerosis, as has recently been proposed for PLA2G5 and PLA2G10.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Section: Pla2g3-treated Ldl Facilitates Macrophage Foam Cell Formatiomentioning

confidence: 99%

See 2 more Smart Citations

Analyses of Group III Secreted Phospholipase A2 Transgenic Mice Reveal Potential Participation of This Enzyme in Plasma Lipoprotein Modification, Macrophage Foam Cell Formation, and Atherosclerosis

Sato

Kato²,

Isogai

et al. 2008

Journal of Biological Chemistry

Self Cite

123

138

View full text Add to dashboard Cite

show abstract

“…Les sPLA2 sont également produites par les cellules de l'immunité naturelle (monocytes/macrophages) et adaptative (lymphocytes T) [9], et par les cellules de la paroi vasculaire [38] ( §). Les sPLA2 des groupes IIA (GIIA), III (GIII) et V (GV) ont été identifiées dans les plaques d'athérosclérose chez la souris et chez l'homme [10]. Les souris géné-tiquement modifiées (inhibition et surexpression) ont permis de montrer que les sPLA2 GIIA, GIII et GV sont pro-athérogènes.…”

Section: Lp-pla2 Et Risque Cardiovasculaireunclassified