Lipoprotein lipase as an attractive target for correcting dyslipidemia and reduction of CVD residual risk

D. A. Dorovsky, A. L. Zagayko


Lipoprotein lipase has long been known to hydrolyse triglycerides from triglycerides-rich lipoproteins. It also the ability to promote the binding of lipoproteins to the wide variation of  lipoprotein receptors. There are some studies that suggest the possible atherogenic role of lipoprotein lipase. In theory, lipoprotein lipase deficiency should help to clarify this question. However, the rarity of this condition means that it has not been possible to conduct epidemiological studies.  During the last decade it became obvious that elevated plasma TG and low HDL-cholesterol are part of CVD residual risk. Thus LPL is an attractive target for correcting dyslipidemia and reduction of CVD residual risk.


Lipoprotein lipase; atherosclerosis; lipoproteins

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Interchange of apolipoproteins between chylomicrons and high-density lipoproteins during alimentary lipemia in man/ Havel R.J., Kane J.P., Kashyap M.L.// J. Clin. Invest.-1973.V.52, P.32-38.

Lipolytic enzymes and plasma lipoprotein metabolism/ Nilsson-Ehle P., Garfinkel A.S., Schotz M.C.// Ann. Rev. Biochem.-1980.V.49, P.667-93.

The metabolic and molecular basis of inherited disease/Scriver C.R., Beaudet A.L., Sly W.S.// New York: Mc. Graw-Hill Inc.-2001.V. 2001, P.2789-2816

Lipoprotein lipase enhances the binding of chylomicrons to low-density lipoprotein receptor-related protein/ Beisiegel U., Weber W., Bengtsson-Olivecrona G.// Proc. Natl. Acad. Sci. U S A.-1991.V. 88: , P.8342-6.

Lipoprotein lipase bound to apolipoprotein B lipoproteins accelerates clearance of postprandial lipoproteins in humans/ Zheng C., Brunzell J.D., Sacks F.M.// Arterioscler. Thromb. Vasc. Biol.-2006.V.26 , P.891-6.

Lipoprotein lipase bound to apolipoprotein B lipoproteins accelerates clearance of postprandial lipoproteins in humans. Cellular catabolism of normal very low density lipoproteins via the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor is induced by the C-terminal domain of lipoprotein lipase/ Chappell D.A., Inoue I., Fry G.L.// J. Biol. Chem.-1994.V. 269, P.18001-6.

A carboxyl-terminal fragment of lipoprotein lipase binds to the low density lipoprotein receptor-related protein and 12 inhibits lipase-mediated uptake of lipoprotein in cells/ Nykjaer A., Nielsen M., Lookene A.//J. Biol. Chem.-1994.V.269 , P.31747-55.

Catalytically inactive lipoprotein lipase expression in muscle of transgenic mice increases very low density lipoprotein uptake: direct evidence that lipoprotein lipase bridging occurs in vivo/ Merkel M., Kako Y., Radner H.// Proc. Natl. Acad. Sci. U S A.-1998.V. 95 , P.13841-6.

Lipoprotein lipase in human plasma is mainly inactive and associated with cholesterol-rich lipoproteins/ Vilella E., Joven J., Fernandez M.// J. Lipid. Res.-1993.V. 34, P.1555-64.

Lipoprotein lipase mass and activity in plasma and their increase after heparin injection/ Tornvall P., Hamsten A., Olivecrona T.// Arterioscler. Thromb. Vasc. Biol.-1995.V. 15, P.1086-93.

Preheparin serum lipoprotein lipase mass level: The effects of age, gender and type of hyperlipidemia/ Watanabe H., Hiroh Y., Shirai K.// Atherosclerosis-1999.V.145 , P.45-50.

High-density lipoprotein: Relations to 13 metabolic parameters and severity of coronary artery disease/ Tornvall P., Karpe F., Proudler A.// Metabolism.-1996.V. 45, P.1375-82.

Defective enzyme protein in lipoprotein lipase deficiency/ Auwerx J.H., Babirak S.P., Brunzell J.D.// Eur. J. Clin. Invest .-1989.V.19, P.433-37.

Identification of lipoprotein lipase immunoreactive protein in pre- and postheparin plasma from normal subjects and patients with type I hyperlipoproteinemia/ Kern P.A., Goldberg I.J., Ong J.M.// J. Lipid. Res.-1990.V. 31 , P.17-26.

Mechanism by which lipoprotein lipase alters cellular metabolism of lipoprotein (a), low density lipoprotein, and nascent lipoproteins: Roles for low density lipoprotein receptors and heparan sulphate proteoglycans/ Williams K.J., Fless G.M., Swenson T.L.// J. Biol. Chem.-1992.V. 267 , P.13284-92.

Measurement of the serum lipoprotein lipase concentration is useful for studying triglyceride metabolism: Comparison with postheparin plasma/ Hirano T., Nishioka F., Murakami T.// Metabolism.-2004.V. 53, P.526-31.

Serum lipoprotein lipase concentration and risk for future coronary artery disease: the EPIC-Norfolk prospective population study/ Rip J., Nierman M.C., Wareham N.J.//Arterioscler. Thromb. Vasc. Biol.-2006.V.26 , P.637-42.

Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity/ Steinberg D., Parthasathary S., Carew T.E.// New Engl. J. Med.-1989.V. 320, P.915–924.

A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis/ Reymer P.W.A., Gagne E., Groenemeyer B.E.// Nature Genet.-1995.V. 10, P.28–34.

A common substitution (Asn291Ser) in lipoprotein lipase is associated with increased risk of ischemic heart disease/ Wittrup H.H., Tybjorg-Hansen A., Abildgaard S.// J. Clin. Invest.-1997.V. 99 , P.1606–1613.

Detection and characterization of the heterozygote state for lipoprotein lipase deficiency/ Babirak S.P., Iverius P.H., Fujimoto W.Y.// Arteriosclerosis-1989.V. 9, P.326–334.

A systematic review and meta-analysis of the relationship between lipoprotein lipase Asn291Ser variant and diseases/ Hu Y., Liu W., Huang R.// J. Lipid.Res.-2006.V. 47, P.1908–1914.

Seven lipoprotein lipase gene polymorphisms, lipid fractions, and coronary disease: a HuGE association review and meta-analysis/Sagoo G.S., Tatt I., Salanti G.//Am. J. Epidemiol.-2008.V. 168, P.1233–1246.

Spontaneous atherosclerosis in aged lipoprotein lipase-deficient mice with severe hypertriglyceridemia on a normal chow diet/ Zhang X., Qi R., Xian X.// Circ. Res.-2008.V. 102, P.250–256.

Overexpression of human lipoprotein lipase in transgenic mice. Resistance to diet-induced hypertriglyceridemia and hypercholesterolemia/ Shimada M., Shimano H., Gotoda T.// J. Biol. Chem.-1993.V. 268, P.17924–17929.

Suppression of diet-induced atherosclerosis in low density lipoprotein receptor knockout mice overexpressing lipoprotein lipase/ Shimada M., Ishibashi S., Inaba T.// Proc. Natl. Acad. Sci. USA.-1996.V. 93, P.7242–7246.

Overexpression of lipoprotein lipase in transgenic rabbits inhibits diet-induced hypercholesterolemia and atherosclerosis/ Fan J., Unoki H., Kojima N.// J. Biol. Chem.-2001.V. 276, P.40071–40079.

The novel compound NO-1886 increases lipoprotein lipase activity with resulting elevation of high density lipoprotein cholesterol, and long-term administration inhibits atherogenesis in the coronary arteries of rats with experimental atherosclerosis/ Tsutsumi K., Inoue Y., Shima A.// J. Clin. Invest.-1993.V. 92, P.411–417.

Lipoprotein lipase mass and activity in severe hypertriglyceridemia/ Kobayashi J., Hashimoto H., Fukamachi I.// Clin. Chim. Acta-1993.V. 216, P.113–123.

Serum lipoprotein lipase mass: clinical significance of its measurement/ Kobayashi J., Nohara A., Kawashiri M.A.// Clin. Chim. Acta-2007.V. 378, P.7–12.

Pre-heparin plasma lipoprotein lipase mass: correlation with intra-abdominal visceral fat accumulation/ Kobayashi J., Saito K., Fukamachi I.// Horm. Metab. Res.-2001.V. 33, P.412–416.

Association between preheparin serum lipoprotein lipase mass and acute myocardial infarction in Japanese men/ Hitsumoto T., Yoshinaga K., Aoyagi K.// J. Atheroscler. Thromb.-2002.V. 9, P.163–169.

Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis/ Hitsumoto T., Ohsawa H., Uchi T.// Atherosclerosis-2000.V. 153, P.391–396.

Comparison of the effect of post-heparin and pre-heparin lipoprotein lipase and hepatic triglyceride lipase on remnant lipoprotein metabolism/ Shirakawa T., Nakajima K., Shimomura Y.// Clin. Chim. Acta-2015.V. 440, P.193–200.

Relation between RLP-triglyceride to RLP-cholesterol ratio and particle size distribution in RLP-cholesterol profiles by HPLC/ Okazaki M., Usui S., Tada N.// Clin. Chim. Acta.-2000.V. 296, P.135–149.

The novel compound NO-1886 increase lipoprotein lipase activity with resulting elevation of high density lipoprotein cholesterol, and long-term administration inhibits atherogenesis in the coronary arteries of rats with experimental atherosclerosis/ Tsutsumi K., Iwasaki K., Kawamura M.// J. Clin. Invest.-1993.V. 92 , P.411-417.

The novel compound NO-1886 elevates plasma high-density lipoprotein cholesterol levels in hamsters and rabbits by increasing lipoprotein lipase without any effect on cholesteryl ester transfer protein activity/ Tsutsumi K., Inoue Y., Murase T.// Metabolism.-1997.V. 46, P.257-260.

High density lipoprotein subfractions in relation to lipoprotein lipase activity of tissues in man – evidence for reciprocal regulation of HDL2 and HDL3 levels by lipoprotein lipase/ Taskinen M.R., Nikkilä E.A.// Clin. Chim. Acta-1981.V. 112, P.325-332.

Plasma lipid transfer proteins/Tall A.R.// Ann. Rev. Biochem.-1995.V. 64, P.235-257.

Differences in plasma cholesteryl ester transfer activity in sixteen vertebrate species/ Ha Y.C., Barter P.J.// Comp. Biochem. Physiol.-1982.V. 71, P. 265-269.

Impaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hypercholesterolemia and atherosclerosis/ Shimokawa H., Vanhoutte P.M.// Circ. Res.-1989.V. 64, P. 900-914.

Myocardial aging: functional alterations and related cellular mechanisms/ Lakatta E.G., Yin F.C.// Am. J. Physiol.-1982.V. 242, P.927-941.

Age-associated decrease in histamine-induced vasodilation may be due to reduction of cyclic GMP formation/ Moritoki H., Iwamoto T., Ishida Y.// Br. J. Pharmacol.-1988.V. 95, P.1015-1022.

A lipoprotein lipase activator, NO-1886, improves endothelium-dependent relaxation of rat aorta associated with aging/ Hara T., Okada K., Sakamoto S.// Eur. J. Pharmacol.-1998.V. 350, P.75-79.

A lipoprotein lipase activator, NO-1886 prevents impaired endothelium-dependent relaxation of aorta caused by exercise in aged rats/ Kusunoki M., Tsutsumi K., Nakamura T.// Exp. Gerontol.-2002.V. 37, P.891-896.

Protective effect of lipoproteins containing apolipoprotein A-I on Cu2+ catalyzed oxidation of human low density lipoprotein/ Ohta T., Takata K., Horiuchi S.// FEBS. Lett.-1989.V. 257, P.435-438.

Antiatherogenic effects of novel lipoprotein lipase-enhancing agent in cholesterol-fed New Zealand White rabbits/ Chiba T., Uetsuka R., Tomita I.// Arterioscler. Thromb. Vasc. Biol.-1997.V. 17, P.2601-2608.

Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver/ Sanderson L. M., Muller M., Kersten S.// Mol. Cell. Biol.-2009.V.29, P. 6257.

Angiopoietin-like protein 4 is a potent hyperlipidemia-inducing factor in mice and inhibitor of lipoprotein lipase/Yoshida K., Ono M., Furukawa H.// J. Lipid. Res.-2002.V. 43, P.1770.

The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity/Mandard S., Muller M., Kersten S.//J. Biol. Chem.-2006, P.281.

Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis/Adachi H.; Oike Y., Araki E.// Biochem. Biophys. Res. Commun.-2009, P

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