Endothelial lipase

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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]

Contents

Discovery

Phospholipids, cholesterol (orange spheres) and two apolipoprotein A-1 chains (pink ribbon) interaction ApoA1+lipids 3K2S.png
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

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 Fat triglyceride shorthand formula.PNG
Triglyceride Structure

Biological Function

Lipid Metabolism Hepatic lipase.jpg
Lipid Metabolism

Metabolism

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

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.

Related Research Articles

Cholesterol Sterol biosynthesized by all animal cells

Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol, a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell membranes. When chemically isolated, it is a yellowish crystalline solid.

High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle and transporting up to hundreds of fat molecules per particle.

Low-density lipoprotein One of the five major groups of lipoprotein

Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein which transport all fat molecules around the body in the extracellular water. These groups, from least dense to most dense, are chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL is involved in atherosclerosis, a process in which it is oxidized within the walls of arteries.

Lipoprotein Biochemical assembly whose purpose is to transport hydrophobic lipid molecules

A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, surrounded by a phospholipid outer shell, with the hydrophilic portions oriented outward toward the surrounding water and lipophilic portions oriented inward toward the lipid center. A special kind of protein, called apolipoprotein, is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role.

Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream. VLDL is assembled in the liver from triglycerides, cholesterol, and apolipoproteins. VLDL is converted in the bloodstream to low-density lipoprotein (LDL) and intermediate-density lipoprotein (IDL). VLDL particles have a diameter of 30–80 nm. VLDL transports endogenous products, whereas chylomicrons transport exogenous (dietary) products. In the early 2010s both the lipid composition and protein composition of this lipoprotein were characterised in great detail.

Chylomicron One of the five major groups of lipoprotein

Chylomicrons, also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85–92%), phospholipids (6–12%), cholesterol (1–3%), and proteins (1–2%). They transport dietary lipids from the intestines to other locations in the body. ULDLs are one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream. A protein specific to chylomicrons is ApoB48.

Intermediate-density lipoproteins (IDLs) belong to the lipoprotein particle family and are formed from the degradation of very low-density lipoproteins as well as high-density lipoproteins. IDL is one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream. Each native IDL particle consists of protein that encircles various lipids, enabling, as a water-soluble particle, these lipids to travel in the aqueous blood environment as part of the fat transport system within the body. Their size is, in general, 25 to 35 nm in diameter, and they contain primarily a range of triglycerides and cholesterol esters. They are cleared from the plasma into the liver by receptor-mediated endocytosis, or further degraded by hepatic lipase to form LDL particles.

Lacteal Lymphatic capillary

A lacteal is a lymphatic capillary that absorbs dietary fats in the villi of the small intestine.

Lipoprotein lipase Mammalian protein found in Homo sapiens

Lipoprotein lipase (LPL) is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water-soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very low-density lipoproteins (VLDL), into two free fatty acids and one monoacylglycerol molecule. It is also involved in promoting the cellular uptake of chylomicron remnants, cholesterol-rich lipoproteins, and free fatty acids. LPL requires ApoC-II as a cofactor.

Hyperlipidemia is abnormally elevated levels of any or all lipids or lipoproteins in the blood. The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding. Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing medication to control blood lipid levels.

Scavenger receptors are a large and diverse superfamily of cell surface receptors. Its properties were first recorded in 1970 by Drs. Brown and Goldstein, with the defining property being the ability to bind and remove modified low density lipoproteins (LDL). Today scavenger receptors are known to be involved in a wide range of processes, such as: homeostasis, apoptosis, inflammatory diseases and pathogen clearance. Scavenger receptors are mainly found on myeloid cells and other cells that bind to numerous ligands, primarily endogenous and modified host-molecules together with pathogen-associated molecular patterns(PAMPs), and remove them. The Kupffer cells in the liver are particularly rich in scavenger receptors, includes SR-A I, SR-A II, and MARCO.

Foam cell Fat-laden M2 macrophages seen in atherosclerosis

Foam cells, also called lipid-laden macrophages, are a type of cell that contain cholesterol. These can form a plaque that can lead to atherosclerosis and trigger heart attacks and stroke.

Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown or storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In animals, these fats are obtained from food or are synthesized by the liver. Lipogenesis is the process of synthesizing these fats. The majority of lipids found in the human body from ingesting food are triglycerides and cholesterol. Other types of lipids found in the body are fatty acids and membrane lipids. Lipid metabolism is often considered as the digestion and absorption process of dietary fat; however, there are two sources of fats that organisms can use to obtain energy: from consumed dietary fats and from stored fat. Vertebrates use both sources of fat to produce energy for organs such as the heart to function. Since lipids are hydrophobic molecules, they need to be solubilized before their metabolism can begin. Lipid metabolism often begins with hydrolysis, which occurs with the help of various enzymes in the digestive system. Lipid metabolism also occurs in plants, though the processes differ in some ways when compared to animals. The second step after the hydrolysis is the absorption of the fatty acids into the epithelial cells of the intestinal wall. In the epithelial cells, fatty acids are packaged and transported to the rest of the body.

Acid lipase disease or deficiency is a name used to describe two related disorders of fatty acid metabolism. Acid lipase disease occurs when the enzyme lysosomal acid lipase that is needed to break down certain fats that are normally digested by the body is lacking or missing. This results in the toxic buildup of these fats in the body's cells and tissues. These fatty substances, called lipids, include waxes, oils, and cholesterol.

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Hepatic lipase Mammalian protein found in Homo sapiens

Hepatic lipase (HL), also called hepatic triglyceride lipase (HTGL) or LIPC, is a form of lipase, catalyzing the hydrolysis of triacylglyceride. Hepatic lipase is coded by chromosome 15 and its gene is also often referred to as HTGL or LIPC. Hepatic lipase is expressed mainly in liver cells, known as hepatocytes, and endothelial cells of the liver. The hepatic lipase can either remain attached to the liver or can unbind from the liver endothelial cells and is free to enter the body's circulation system. When bound on the endothelial cells of the liver, it is often found bound to HSPG, heparan sulfate proteoglycans (HSPG), keeping HL inactive and unable to bind to HDL or IDL. When it is free in the bloodstream, however, it is found associated with HDL to maintain it inactive. This is because the triacylglycerides in HDL serve as a substrate, but the lipoprotein contains proteins around the triacylglycerides that can prevent the triacylglycerides from being broken down by HL.

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References

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  8. 1 2 3 "Atherosclerosis | National Heart, Lung, and Blood Institute (NHLBI)". www.nhlbi.nih.gov. Retrieved 2019-04-11.
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