Disease relevance of LIPG

• To investigate the effects of EDL on binding and uptake of high-density lipoprotein (HDL), as well as on the selective uptake of HDL-derived cholesterol esters (CEs), HepG2 cells were infected with adenovirus coding for EDL [1].
• Plasma EL concentrations were positively correlated with various indices of obesity, fasting plasma insulin, and plasma CRP, IL-6, and sPLA(2)-IIA concentrations [2].
• Its tissue-restricted pattern of expression and its ability to be expressed by endothelial cells, suggests that endothelial cell-derived lipase may have unique functions in lipoprotein metabolism and in vascular disease [3].
• Molecular analysis of the plasmid-encoded hemolysin of Escherichia coli O157:H7 strain EDL 933 [4].
• A dose of 25 microg kg(-1) day(-1) of formoterol elicited greater EDL and soleus hypertrophy than salmeterol, but resulted in similar beta-adrenoceptor downregulation [5].

Psychiatry related information on LIPG

• EDL and FDL display distinctive, individualized patterns of locomotor activity that may vary in a facultative manner or in different forms of locomotion (O'Donovan et al., 1980; Trank et al., 1996) [6].

High impact information on LIPG

• In contrast to other family members, this new lipase is synthesized by endothelial cells in vitro and thus has been termed endothelial lipase (encoded by the LIPG gene) [7].
• EL has substantial phospholipase activity, but less triglyceride lipase activity [7].
• EL is expressed in vivo in organs including liver, lung, kidney and placenta, but not in skeletal muscle [7].
• Fatty acids produced by EL activity were absorbed by adipocytes and incorporated into the TG moiety of AT [8].
• To determine EL's role in humans, we find a significant association between a single-nucleotide polymorphism 584C/T in the EL (LIPG) gene and HDL cholesterol in a well characterized population of 372 individuals [9].

Biological context of LIPG

• Thus our results demonstrate that EDL mediates both HDL binding and uptake, and the selective uptake of HDL-CE, independently of lipolysis and CLA-1 [1].
• CONCLUSIONS: These results suggest that EDL may have unique functional roles in the pathogenesis of coronary artery diseases such as atherosclerosis as well as in lipid metabolism in the vessel wall [10].
• This study examined associations of LIPG haplotypes, comprising a single nucleotide polymorphism (SNP) in the promoter region (-384A>C), and a nonsynonymous SNP in exon 3 (Thr111Ile or 584C>T), with lipoprotein risk factors in 541 adult Japanese Americans [11].
• The LIPG gene on chromosome 18 encodes for endothelial lipase, a member of the triglyceride lipase family [11].
• We conclude that the LIPG genotype is associated with interindividual variability in HDL-C and its subfractions and their response to exercise training [12].

Anatomical context of LIPG

• The aim of this study was to investigate the local expression of EDL in human coronary arteries [10].
• In addition, EDL was expressed in infiltrating cells within atheromatous plaques as well as endothelial and smooth muscle cells [10].
• Double labeling immunofluorescence confirmed EDL positive-cells were endothelial cells, smooth muscle cells and macrophages [10].
• The combined impact of visceral adipose tissue (VAT) and of an inflammation score on EL concentrations was investigated [2].
• Immunohistochemistry showed EL protein in syncytiotrophoblasts facing the maternal blood and endothelial cells facing the fetal blood in placentas from both normal women and women with diabetes [13].

Associations of LIPG with chemical compounds

• EDL is a phospholipase with very little triacylglycerol lipase activity [1].
• Inhibition of the enzymic activity with tetrahydrolipstatin (THL) significantly enhanced the effect of EDL, as reflected by a 5.2-fold increase in binding, a 2.6-fold increase in particle uptake and a 1.1-fold increase in CE selective uptake compared with incubations without THL [1].
• In summary, EL mediates binding and uptake of plasma lipoproteins via a process that is independent of its enzymatic activity, requires cellular heparan sulfate proteoglycans, and is regulated by ligand clustering [14].
• Inhibition of proteoglycan sulfation by sodium chlorate or incubation of cells with labeled lipoproteins in the presence of heparin (100 microg/ml) abolished bridging effects of EL [14].
• In situ hybridization studies demonstrated intense EL mRNA staining of lutein cells in corpora lutei in ovaries, of spermatocytes in the late pachytene and diplotene stages in testes, and of principal cells in epididymis [15].

Other interactions of LIPG

• Despite 1.7-fold higher binding and 1.8-fold higher holoparticle uptake, the selective CE uptake by MUT-EDL-expressing cells was comparable with EDL-expressing cells and was even decreased 1.3-fold with THL [1].
• When entered into the model, LPL activity accounted for 16.1% (P < 0.0001) and plasma CRP concentrations accounted for 20.9% (P < 0.0001) of the variance in EL concentrations [2].
• Like LPL but not HL, both lipase activities of EL were inhibited by 1 M NaCl [16].
• Multiple regression analyses revealed that plasma CRP concentrations explained 14.5% (P = 0.0008) of the variance in EL concentrations [2].
• Relative to the serum before overexpression of EL, the efflux potential of the serum via SR-BI decreased by 90% and ABCA1-mediated efflux increased by 63% [17].

Analytical, diagnostic and therapeutic context of LIPG

• We have inactivated EL in mice by gene targeting [9].
• METHODS AND RESULTS: Human coronary arterial specimens from 10 autopsied cases were examined by immunohistochemistry with polyclonal antibodies against specific synthetic EDL peptides [10].
• In situ hybridization studies on E10.5 whole embryos and embryonic sections showed expression of EL mRNA in multiple tissues, although of varying intensity [15].
• When placental protein extracts were separated by heparin-Sepharose affinity chromatography, the EL protein eluted as a single peak without detectable phospholipid or triglyceride (TG) lipase activity [18].
• Reduction in molecular mass of EL after treatment with glycosidases and after treatment of EL-expressing cells with the glycosylation inhibitor tunicamycin demonstrated that EL is a glycosylated protein [19].

References