Endothelial lipoprotein lipase

In the enterocyte, provitamin A carotenoids are immediately converted to vitamin A esters. Carotenoids, vitamin A esters, and other lipophilic compounds are packaged into chylomicrons, which are secreted into lymph and then into the bloodstream. Chylomicrons are attacked by endothelial lipoprotein lipases in the bloodstream, leading to chylomicron remnants, which are taken up by the liver (van den Berg and others 2000). Carotenoids are exported from liver to various tissues by lipoproteins. Carotenes (such as (3-carotene and lycopene) are transported by low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL), whereas xanthophylls (such as lutein, zeax-anthin, and (3-cryptoxanthin) are transported by high-density lipoproteins (HDL) and LDL (Furr and Clark 1997). 

Lipoprotein metabolism. Entero-cytes release absorbed lipids in the form of triglyceride-rich chylomicrons. Bypassing the liver, these enter the circulation mainly via the lymph and are hydrolyzed by extrahepatic endothelial lipoprotein lipases to liberate fatty acids. The remnant particles move on into liver cells and supply these with cholesterol of dietary origin. 

Nicotinic acid and its derivatives (pyridylcarbinol, xanthinol nicotinate, acipimox) activate endothelial lipoprotein lipase and thereby lower triglyceride levels. At the start of therapy, a prostaglandin-mediated vasodilation occurs (flushing and hypotension) that can be prevented by low doses of acetyl-salicylic acid. 

The size of the VLDL particle in plasma diminishes and its density increases as triglyceride is hydrolyzed by endothelial lipoprotein lipase, and the particles are thus converted to intermediate-density lipoproteins (IDL) (B32, S35). The IDL detach from the endothelium, and some are taken up by hepatic B-100, E receptors. The remaining particles in the circulation are further depleted of some cholesteryl ester (by an unknown mechanism), and most of the remaining triglyceride (probably by hepatic triglyceride lipase, in the liver sinusoids) (D5). Hie resulting LDL particles are largely composed of cholesteryl ester as the core lipid and apoB-100 as the apolipoprotein. 

Z7. Zilversmit, D. B., A proposal linking atherogenesis to the interaction of endothelial lipoprotein lipase with triglyceride-rich lipoproteins. Circ. Res. 33, 633-638 (1973). 

TNF (17.5) Monocyte/macrophage, lymphocyte, neutrophil, endothelium, fibroblast, keratinocyte Activation of T and B cells, natural killer cells, neutrophils, and osteoblasts. Stimulation of endothelial cells to release chemotactic proteins, NO and PGI2. Tumoricidal activity. Induces fever, sleep, hepatic acute phase protein synthesis, catabolism, ACTH release. Lead to myocardial depression, hypotension/shock, hypercoagulability, and death. Stimulates production of IL-1, IL-6, IL-8, IFN-y, and H202. Suppression of cytochrome P-450, thyroglobulin, and lipoprotein lipase. Induces complement activation, release of eicosanoids, including PAF. Procoagulant activity. 

Lipoprotein lipase (LPL) Local enzymatic Endothelial cells within adipose tissue Lipoprotein-triglyceride hydrolysis... 

The physiological function of heparin is not completely understood. It is found only in trace amounts in normal circulating blood. It exerts an antihpemic effect by releasing lipoprotein lipase from endothehal cells heparinlike proteoglycans produced by endothelial cells have anticoagulant activity. Heparin decreases platelet and inflammatory cell adhesiveness to endothelial cells, reduces the release of platelet-derived growth factor, inhibits tumor cell metastasis, and exerts an antiproliferative effect on several types of smooth muscle. 

Relevant heparin-binding enzymes not involved in the coagulation cascade are, for example, elastase, cathepsin G, superoxide dismutase, lipoprotein lipase and other lipases. The plasma clearing properties of heparin are associated with its binding to lipoprotein lipase and hepatic lipase when the enzymes are released from the surface of endothelial cells [11] and have been studied in view of a potential impact on the regulation of atherosclerosis. 

The chylomicrons are delivered to other tissues in the body via the bloodstream. In the tissues the chylomicrons bind to the endothelial cells of the capillaries and are degraded to fatty acids and glycerol by lipoprotein lipase. This enzyme is secreted by cells in the tissue and is bound to the endothelial cells. 

Paradis E., Clavel S., Julien P., Murthy M. R. V., de Bilbao F., Arsenijevic D., Giannakopoulos P., Vallet P., and Richard D. (2004). Lipoprotein lipase and endothelial lipase expression in mouse brain regional distribution and selective induction following kainic acid-induced lesion and focal cerebral ischemia. Neurobiol. Dis. 15 312-325. 

LRP is a member of the LDL receptor gene family (ref. 649) and, like the LDL receptor, performs an essential role in the removal of certain lipoprotein particles from the bloodstream. As Heeren et al. (ref. 650) explain, triglycerides are transported mainly by two distinct classes of lipoproteins, the chylomicrons and the very-low-density lipoproteins (VLDL). After assembly in the intestine, chylomicrons are carried via lymph into the bloodstream, where they are transformed at the endothelial surface to remnant lipoproteins through the catalytic action of lipoprotein lipase (for review, see ref. 651,652). After lipolysis, the lipoprotein lipase remains associated with the chylomicron remnants and, in conjunction with apolipoprotein E (apo E) (ref. 653-655), facilitates their clearance by the liver into hepatocytes (ref. 656) via LDL receptors and the LRP (ref. 657-660). (The essential role for both receptors in chylomicron remnant removal in vivo has been demonstrated in gene knockout and gene transfer experiments (ref. 661,662 for review, see ref. 663).)... 

Chylomicrons are triglyceride rich and contain apolipoprotein B-48 and the A types. The latter are synthesized in the intestinal tract cells. Additional apoproteins are transferred to the chylomicrons from HDL in circulation the apoE and apoC types. Their site of synthesis is the liver. The chylomicrons are subject to degradation by lipoprotein lipase in the peripheral tissue, especially adipose tissue. Lipoprotein lipase activity is increased by increased blood insulin levels. This enzyme is extracellular, attached to the capillary endothelial cells, and activated by ApoC-II, which is present in the chylomicrons. Lipoprotein lipase causes the hydrolysis of triglycerides, thus decreasing chylomicron size... 

Shimada, K., Lanzillo, J.J., Douglas, W.H.J., Fanburg, B.L. 1982. Stabilization of lipoprotein lipase by endothelial cells. Biochim. Biophys. Acta 710, 117-21. 

Vitamin E, like neutral lipids, requires apoB lipoproteins at every stage of its transport (Fig. 27-2). Dietary vitamin E becomes emulsified in micelles produced during the digestive phase of lipid absorption and permeates the intestinal epithelium, similar to fatty acids and cholesterol. Uptake of vitamin E by enterocytes appears to be concentration dependent. Within intestinal cells, vitamin E is packaged into chylomicrons and secreted into lymph. During blood circulation of chylomicrons, some vitamin E may be released to the tissues as a consequence of partial lipolysis of these particles by endothelial cell-anchored lipoprotein lipase. The rest remains associated with chylomicron remnants. Remnant particles are mainly endocy-tosed by the liver and degraded, resulting in the release of fat-soluble vitamins. 

Chylomicrons are produced from dietary fat by the removal of resynthesised triglycerides from the mucosal cells of the small intestine into the intestinal lumen. These then enter the circulation via the thoracic dncts in the lymphatic system and enter into the subclavian veins, where triglyceride content is reduced by the action of lipoprotein lipases (LPL) on capillary endothelial surfaces in skeletal muscle and fat. The free fatty acids (FFA) from the triglycerides are used by the tissues as an energy source or stored as triglycerides. The chylomicron remnants, stripped of triglyceride and therefore denser, are then taken up by the liver by LDL receptor-mediated endocytosis, thereby delivering cholesterol to the liver. 

The liver synthesizes two enzymes involved in intra-plasmic lipid metabolism hepatic triglyceride lipase (HTL) and lecithin-cholesterol-acyltransferase (LCAT). The liver is further involved in the modification of circulatory lipoproteins as the site of synthesis for cholesterol-ester transfer protein (CETP). Free fatty acids are in general potentially toxic to the liver cell. Therefore they are immobilized by being bound to the intrinsic hepatic fatty acid-binding protein (hFABP) in the cytosol. The activity of this protein is stimulated by oestrogens and inhibited by testosterone. Peripheral lipoprotein lipase (LPL), which is required for the regulation of lipid metabolism, is synthesized in the endothelial cells (mainly in the fatty tissue and musculature). 

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