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Endothelial lipase

Endothelial Lipase
Identifiers
SymbolLIPG
Alt. symbolsEL

Endothelial lipase (LIPG) is a form of lipase secreted by vascular endothelial cells in tissues with high metabolic rates and vascularization, such as the liver, lung, kidney, and thyroid gland.[1] The LIPG enzyme is a vital component to many biological processes. These processes include lipoprotein metabolism, cytokine expression, and lipid composition in cells.[1] Unlike the lipases that hydrolyze Triglycerides, endothelial lipase primarily hydrolyzes phospholipids.[1] Due to the hydrolysis specificity, endothelial lipase contributes to multiple vital systems within the body. On the contrary to the beneficial roles that LIPG plays within the body, endothelial lipase is thought to play a potential role in cancer and inflammation.[1] Knowledge obtained in vitro and in vivo suggest the relations to these conditions, but human interaction knowledge lacks due to the recent discovery of endothelial lipase.[2] Endothelial lipase was first characterized in 1999.[3] The two independent research groups which are notable for this discovery cloned the endothelial lipase gene and identified the novel lipase secreted from endothelial cells.[2] The anti-Atherosclerosis opportunity through alleviating plaque blockage and prospective ability to raise High-density lipoprotein (HDL) have gained endothelial lipase recognition.[4]

Discovery

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Phospholipids, cholesterol (orange spheres) and two apolipoprotein A-1 chains (pink ribbon) interaction

In 1999, the identification of endothelial lipase was independently discovered by two research groups.[2]

The first group at Rhone-Poulenc Rorer cloned and characterized a new member of the triacylglyerol (TG) family. When this novel endothelial lipase was over-expressed in mice, the concentrations of HDL Cholesterol and apolipoprotein A-I in plasma decreased.[3]

A second group at Stanford University independently cloned this same endothelial lipase from human umbilical vein endothelial cells, human coronary artery endothelial cells and rodent endothelial-like yolk sacs.[5] Suppression subtractive hybridization was used to isolate the genes.[5] The genes were then compared and aligned. Two cDNA fragments expressed the lipase gene and endothelial properties.[5] Northern blot analysis documented the samples.[5] The suggested relation to metabolism and vascular disease was attributed to tissue selective expression in endothelial cells.[5]

Structure

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Endothelial lipase is a protein that belongs triglyceride lipase category.[1] This protein is encoded by the LIPG gene.[1] Endothelial lipase is secreted from vascular endothelial cells, being the only lipase to date.[3] The primary secretion is that of a 55kDa protein which is secreted to a 68kDa protein after post-translational Glycosylation.[1] LIPG functions as it binds to Proteoglycans.[1] LIPG also has the potential for additional cleavage.[1] The additional cleavage would result in inactivity of the 40 kDa protein N-terminal 40 kDa and 28 kDa C-terminal.[1] LIPG has the capability to form a protein dimer prior to secretion which causes dimerization to appear.[1] The addition reaction of the same compound and molecules enhances the resistance to cleavage and limited activity is sustained.[1]

Triglyceride Structure

Biological Function

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Lipid Metabolism

Metabolism

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The site of endothelial lipase enzymatic activity is the surface of endothelial cells. LIPG regulates lipoprotein metabolism through the hydrolysis of HDL phospholipids.[4] This high-density lipoprotein is an amphipathic lipid, meaning the lipid is composed of both a hydrophobic and a hydrophilic component.[6] Cholesterol has a four-ring structure and is an isoprenoid-based hydrocarbon.[6] Although cholesterol lacks the phosphate head group, cholesterol's hydroxyl component interacts with water, categorizing cholesterol as amphipathic.[6] HDL cholesterol provides extreme benefits to the body and is vital in sustaining the fluidity of natural membranes.[6] HDL cholesterol must be maintained at a certain level to ensure normal cell growth and reproduction. The HDL capability of absorption of cholesterol and transport to the liver, aids in the removal of cholesterol in the body.[7] On the contrary, Low-density lipoprotein (LDL) cholesterol works in opposition. LDL cholesterol does not transport cholesterol out of the body but rather serves as a foundation for cholesterol buildup.[7] LDL should be kept low in the body to avoid cholesterol buildup in arteries. When HDL are hydrolyzed, the turnover rate of HDL increases and cholesterol levels in plasma decrease.[4] This hydrolysis allows for the acceleration or continuation of cholesterol removal from the body to avoid a buildup. Following the hydrolysis of HDL, free fatty acid lipid precursors are taken up.[1] These lipids are then utilized in other phospholipid catabolism.[1] In summation, endothelial lipase is said to be a pivotal component in metabolism through high-density lipoprotein hydrolysis.

Vascular Biology

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Endothelial lipase is linked to potential treatment and improvement of atherosclerosis. Atherosclerosis is a vascular disease which is caused by arterial plaque buildup.[8] Cholesterol, fat, calcium, and other components contribute to the formation of plaque in the blood.[8] Plaque is detrimental to vascular heath because it narrows and stiffens the arteries, causing a lack of oxygen-rich blood flow.[8] HDL increase serves as a treatment for atherosclerosis. The hydrolysis of HDL leads to the transportation of cholesterol to the liver.[7] The filtration system of the liver aids in the removal of cholesterol from the body. Therefore, the cholesterol level in the plasma will decrease. Thus, endothelial lipase synthesis of HDL could provide an adequate opportunity to increase HDL levels. Data suggests that endothelial lipase inhibition should increase the plasma HDL, primarily in patients with low HDL-C levels.[4] An increased risk of atherosclerosis is associated with low levels of HDL.[4] Although a functional correlation can be drawn, there is little clinical evidence to provide support to the suggested potential benefits in vascular pathophysiology.

References

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  1. ^ a b c d e f g h i j k l m n Yu JE, Han SY, Wolfson B, Zhou Q (January 2018). "The role of endothelial lipase in lipid metabolism, inflammation, and cancer". Histology and Histopathology. 33 (1): 1–10. doi:10.14670/HH-11-905. PMC 5858721. PMID 28540715.
  2. ^ a b c Paradis ME, Lamarche B (February 2006). "Endothelial lipase: its role in cardiovascular disease". The Canadian Journal of Cardiology. 22 Suppl B (Suppl B): 31B–34B. doi:10.1016/S0828-282X(06)70984-9. PMC 2780840. PMID 16498510.
  3. ^ a b c Jaye M, Lynch KJ, Krawiec J, Marchadier D, Maugeais C, Doan K, South V, Amin D, Perrone M, Rader DJ (April 1999). "A novel endothelial-derived lipase that modulates HDL metabolism". Nature Genetics. 21 (4): 424–8. doi:10.1038/7766. PMID 10192396. S2CID 20658953.
  4. ^ a b c d e Darrow AL, Olson MW, Xin H, Burke SL, Smith C, Schalk-Hihi C, Williams R, Bayoumy SS, Deckman IC, Todd MJ, Damiano BP, Connelly MA (February 2011). "A novel fluorogenic substrate for the measurement of endothelial lipase activity". Journal of Lipid Research. 52 (2): 374–82. doi:10.1194/jlr.D007971. PMC 3023558. PMID 21062953.
  5. ^ a b c d e Hirata K, Dichek HL, Cioffi JA, Choi SY, Leeper NJ, Quintana L, Kronmal GS, Cooper AD, Quertermous T (May 1999). "Cloning of a unique lipase from endothelial cells extends the lipase gene family". The Journal of Biological Chemistry. 274 (20): 14170–5. doi:10.1074/jbc.274.20.14170. PMID 10318835.
  6. ^ a b c d Lodish H, Berk A, Kaiser C, Krieger M, Bretscher A, Ploegh H, Amon A, Martin K (2016). Molecular Cell Biology (8 ed.). New York: W.H. Freeman and Company. pp. 273–282. ISBN 9781464183393. OCLC 1003278428.
  7. ^ a b c CDC (2017-10-31). "LDL and HDL Cholesterol: "Bad" and "Good" Cholesterol". Centers for Disease Control and Prevention. Retrieved 2019-04-11.
  8. ^ a b c "Atherosclerosis | National Heart, Lung, and Blood Institute (NHLBI)". www.nhlbi.nih.gov. Retrieved 2019-04-11.
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Cell biology