Disease relevance of Lipg

• Remarkably, after focal cerebral ischemia, the expression of EL was unaffected whereas a dramatic increase in LPL expression was observed in neocortical areas of the lesioned side of the brain [1].
• These results show that LPL and EL transcripts are selectively upregulated in function of the type of brain injury [1].
• These data suggest a role for EL in the development of atherosclerotic vascular disease [2].
• Furthermore, to test whether EL could play a role in atherogenesis, the expression of EL in the aorta and liver of apolipoprotein E knockout (EKO) mice was determined [3].
• 4. For mdx mice of all ages, muscle hypertrophy was highly effective in the maintenance of control values for absolute force for both EDL and soleus muscles and for absolute power of soleus muscles [4].

High impact information on Lipg

• Endothelial lipase provides an alternative pathway for FFA uptake in lipoprotein lipase-deficient mouse adipose tissue [5].
• Evaluation of these alleles in a C57Bl/6 background revealed an inverse relationship between HDL cholesterol level and EL expression [6].
• A new member of the lipase gene family, initially termed endothelial lipase (gene nomenclature, LIPG; protein, EL), is expressed in a variety of different tissues, suggesting a general role in lipid metabolism [6].
• The ability of muscles from Glut 4-null mice to take up and metabolize glucose has been studied in the isolated white EDL and red soleus muscles [7].
• In EDL muscles from male or female Glut 4-null mice, basal deoxyglucose uptake was lower than in control muscles and was not stimulated by insulin [7].

Chemical compound and disease context of Lipg

• Lipoprotein lipase and endothelial lipase expression in mouse brain: regional distribution and selective induction following kainic acid-induced lesion and focal cerebral ischemia [1].
• EDL muscles were freeze-clamped at rest (n = 10) and during the recovery phase, 1 min after the onset of the tetanus (n = 10), to determine lactate and creatine phosphate [8].
• Differential hindlimb muscle atrophy (soleus greater than plantaris = gastrocnemius greater than EDL) and increased excretion of urea and ammonia were also noted in suspended mice [9].

Biological context of Lipg

• To investigate potential mechanisms by which macrophage-derived lipase expression may mediate proatherogenic effects, we used lentivirus-mediated RNA interference to suppress the expression of either LPL or EL within THP-1 macrophages [10].
• A survey of lipid homeostasis in EL+/+ and EL-/- macrophages revealed that oxidized LDL-induced ABCA1 was attenuated in EL-/- macrophages [11].
• Structural basis of endothelial lipase tropism for HDL [12].
• The phenotype of mice missing both E- and L-selectins (EL(-/-)) is less severe than those seen in the other double knockouts [13].
• In male MLC-GLUT4 EDL, increased glucose influx predominantly led to increased glycolysis [14].

Anatomical context of Lipg

• These results provide further insight into the specific metabolic and potential pathological roles of LPL and EL in human macrophages [10].
• Endothelial lipase (EL) mRNA expression was restricted to CA3 pyramidal cells of the hippocampus, to ependymal cells in the ventral part of the third ventricle and to some cortical cell layers [1].
• Upon injection of KA, a rapid increase in EL mRNA expression was observed in the piriform cortex, hippocampus, thalamus and neocortex [1].
• Endothelial lipase modulates monocyte adhesion to the vessel wall. A potential role in inflammation [15].
• Immunohistochemistry and protein blot studies revealed increased EL expression in the atherosclerotic aortas of the apoE knockout animals [2].

Associations of Lipg with chemical compounds

• EL inactivation had no effect on hepatic mRNAs of proteins involved in reverse cholesterol transport [11].
• Here, we describe fluorescent Bodipy-labeled substrates that can be used in homogeneous, ultra-high-throughput kinetic assays that measure EL phospholipase or triglyceride lipase activities [16].
• These results indicate that while EDL muscles behaved as expected, soleus muscles were able to take up a large amount of glucose in the absence (males) or the presence of insulin (females) [7].
• Mature endothelial lipase (EL) is a 68 kDa glycoprotein [17].
• Single fibres from the extensor digitorum longus (EDL, fast-twitch) and soleus (SOL, mixed fast- and slow-twitch) muscles were attached to a sensitive force-recording apparatus, and activated in Ca(2+)- and Sr(2+)-buffered solutions [18].

Regulatory relationships of Lipg

• High-density lipoprotein hydrolysis by endothelial lipase activates PPARalpha: a candidate mechanism for high-density lipoprotein-mediated repression of leukocyte adhesion [19].

Other interactions of Lipg

• Endothelial lipase modulates HDL but has no effect on atherosclerosis development in apoE-/- and LDLR-/- mice [11].
• We found no difference in aortic atherosclerotic lesion areas between 26-week-old EL+/+ apolipoprotein E-deficient (apoE-/-) and EL-/- apoE-/- mice [11].
• The mapped regions contain several genes involved in the angiogenic process including matrix metalloproteinase 16, eph receptor A7, angiopoetin 1, endothelial lipase, and autotaxin [20].
• In conclusion, the CRD of PC5A and PACE4 functions as a cell surface anchor favoring the processing of their cognate surface-anchored substrates, including endothelial lipase [21].
• Increased expression of endothelial lipase in rat models of hypertension [22].

Analytical, diagnostic and therapeutic context of Lipg

• To assess the hypothesis that EL plays a physiological role in lipoprotein metabolism in vivo, we have used gene targeting of the native murine locus and transgenic introduction of the human LIPG locus in mice to modulate the level of EL expression [6].
• By in situ hybridization, EL mRNA was present only in endothelial cells in liver sections [3].
• In the adult fast EDL, denervation leads to rapid atrophy of IIb fibers and a significant decline in levels of c-ski mRNA [23].
• Moreover, in situ two-color immunofluorescence staining for cytoplasmic collagen IV and surface KL suggests that EL cells are the exclusive source of membrane-bound KL in mouse cultures [24].
• Po was lower in the EDL and soleus muscles from the 48-hour group compared with the control group animals [25].

References