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“Liver-targeted Angptl4 silencing by antisense oligonucleotide treatment attenuates hyperlipidaemia and atherosclerosis development in APOE*3-Leiden.CETP mice”
Cardiovasc Res . 2024 Dec 31;120(17):2179-2190. doi: 10.1093/cvr/cvae195
Melanie Modder  ^{1   2} , Wietse In Het Panhuis  ^{1   2} , Mohan Li  ^{1   2} , Salwa Afkir  ^{1   2} , Alexandra L Dorn  ^{1   2} , Amanda C M Pronk  ^{1   2} , Trea C M Streefland  ^{1   2} , Reshma A Lalai  ^{1   2} , Stefan Pierrou  ³ , Stefan K Nilsson  ³ , Gunilla Olivecrona  ^{3   4} , Sander Kooijman  ^{1   2} , Patrick C N Rensen  ^{1   2} , Milena Schönke  ^{1   2}

“ANGPTL4 silencing via antisense oligonucleotides reduces plasma triglycerides and glucose in mice without causing lymphadenopathy”
J Lipid Res . 2022 Jul;63(7):100237. doi: 10.1016/j.jlr.2022.100237. Epub 2022 Jun 3.
Mingjuan Deng  ¹ , Elda Kutrolli  ² , Anne Sadewasser  ³ , Sven Michel  ³ , Masoumeh Motamedi Joibari  ² , Frank Jaschinski  ³ , Gunilla Olivecrona  ⁴ , Stefan K Nilsson  ² , Sander Kersten  ⁵

“Drug-target Mendelian randomization analysis supports lowering plasma ANGPTL3, ANGPTL4, and APOC3 levels as strategies for reducing cardiovascular disease risk”.
Landfors, F., Henneman, P., Chorell, E., Nilsson, S.K., Kersten, S.
European Heart Journal Open, Volume 4, Issue 3, May 2024, oeae035, doi: 10.1093/ehjopen/oeae035

Scientific background

“Lysosomal lipoprotein processing in endothelial cells stimulates adipose tissue thermogenic adaptation".
Fischer, A.W., Jaeckstein, M.Y., Gottschling, K., Heine, M., Sass, F., Mangels, N., Schlein, C., Worthmann, A., Bruns, O.T., Yuan, Y., Zhu, H., Chen, O., Ittrich, H., Nilsson, S.K., Stefanicka, P., Ukropec, J., Balaz, M., Dong, H., Sun, W., Reimer, R., Scheja, L., Heeren,
Cell Metabolism, online Dec 22, 2020, doi: 10.1016/j.cmet.2020.12.001

“On the mechanism of angiopoietin-like protein 8 for control of lipoprotein lipase activity”.
Kovrov, O., Kristensen, K.K., Larsson, E., Ploug, M., Olivecrona, G..
Journal of Lipid Research. 60:783–793, April 2019, doi: 10.1194/jlr.M088807

“Lipoprotein lipase in mouse kidney: effects of nutritional status and high-fat diet”.
Nyrén, R., Makoveichuk, E., Malla, S., Kersten, S., Nilsson, S.K., Ericsson, M., Olivecrona, G.
American Journal of Physiology-Renal Physiology. 316:F558-F571, Jan 2019, doi: 10.1152/ajprenal.00474.2018.

“TNF-α decreases lipoprotein lipase activity in 3T3-L1 adipocytes by up-regulation of angiopoietin-like protein 4”.
Makoveichuk, E., Vorrsjö, E., Olivecrona, T., Olivecrona, G.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1862:533-540, 2017, doi: 10.1016/j.bbalip.2017.02.005

“Lipoprotein lipase activity and interactions studied in human plasma by isothermal titration calorimetry”.
Reimund, M., Kovrov, O., Olivecrona, G., Lookene, A.
Journal of Lipid Research. 58:279-288, 2017, doi: 10.1194/jlr.D071787.

“Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport”.
Bartelt, A., John, C., Schaltenberg, N., Berbée, J.F.P., Worthmann, A., Cherradi, M.L., Schlein, C., Piepenburg, J., Boon, M.R., Rinninger, F., Heine, M., Toedter, K., Niemeier, A., Nilsson, S.K., Fischer, M., Wijers, S.L., van Marken Lichtenbeldt, W., Scheja, L., Rensen, P.C.N., Heeren,
Nature Communications. 8:15010, 2017, doi:10.1038/ncomms15010.

“The tissue distribution of lipoprotein lipase determines where chylomicrons bind”.
Savonen, R., Hiden, M. Hultin, M., Zechner, R., Levak-Frank, S., Olivecrona, G., Olivecrona, T. 
Journal of Lipid Research, 56:588-598, 2015, 10.1194/jlr.M056028

”Apolipoprotein CIII links insulin resistance to b-cell failure in diabetes”.  
Åvall, K., Alli, Y., Leibiger, I.B., Leibiger, B., Moede, T., Paschen, M., Dicker, A., Daré, E., Köhler, M., Ilegems, E., Abdulreda, M.H., Graham, M., Crooke, R.M., Tay, V.S.Y., Refai, E., Nilsson, S.K., Jacob, S., Selander, L., Berggren, P.-O., Juntti-Berggren, L.
The Proceedings of the National Academy of Sciences (PNAS), USA, 112:E2611-E2619, 2015, doi: 10.1073/pnas.1423849112.

“Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise”, Catoire, M., Alex, S., Paraskevopulos, N., Mattijssen, F., Evers-van Gogh, I., Schaart, G., Jeppesen, J., Kneppers, A., Mensink, M., Voshol, P.J., Olivecrona, G., Soon Tan, N., Hesselink, M.K.C., Berbée, J.F., Rensen, P.C.N., Kalkhoven, E., Schrauwen, P., Kersten, S.. The Proceedings of the National Academy of Sciences, USA, 111:E1043-1052, 2014, doi: 10.1073/pnas.1400889111.

“Structural and functional analysis of APOA5 mutations identified in patients with severe hypertriglyceridemia”.
Mendoza-Barbera, E., Julve, J., Nilsson, S.K., Lookene, A., Martín-Campos, J.M., Roig, R., Lechuga-Sancho, A.M., Sloan, J.H., Fuentes-Prior, P., Blanco-Vaca, F.
Journal of Lipid Research, 54:649-661, 2013, doi: 10.1016/j.bbrc.2014.06.114.

“Apolipoprotein C-I and C-III inhibit lipoprotein lipase activity by displacement of the enzyme from lipid droplets”.
Larsson, M., Vorrsjo, E., Talmud, P., Lookene, A., Olivecrona G..
Journal of Biological Chemistry, 288:33997-40008, 2013, doi: 10.1074/jbc.M113.495366.

“Localization of lipoprotein lipase and GPHBP1 in mouse pancreas: effects of diet and leptin deficiency“.
Nyrén, R., Chang, C.L., Lindström, P., Barmina, A., Vorrsjö, E., Ali, Y., Juntti-Berggren, L., Bensadoun, A., Young, S.G., Olivecrona, T., Olivecrona, G..
BMC Physiology. 12:14, 2012, doi: 10.1186/1472-6793-12-14.

“Linking nutritional regulation of ANGPTL4, GPIHBP1, and LMF1 to lipoprotein lipase activity in rodent adipose tissue”.
Kroupa, O., Vorrsjö, E., Stienstra, R., Mattijssen, F., Nilsson, S.K., Sukonina, V., Kersten, S., Olivecrona, G., Olivecrona, T.
BMC Physiology. 12:13, 2012, doi: 10.1186/1472-6793-12-13.

“Triacylglycerol-rich lipoproteins protect lipoprotein lipase from inactivation by ANGPTL3 and ANGPTL4”.
Nilsson, S.K., Anderson, F., Ericsson, M., Larsson, M., Makoveichuk, E., Lookene, A., Heeren, J., Olivecrona, G..
Biochim Biophys Acta. 1821:1370-1378, 2012, doi:10.1016/j.bbalip.2012.06.003.

“Impaired LDL receptor-related protein 1 translocation correlates with improved dyslipidemia and atherosclerosis in apoE-deficient mice”.
Gordts, P.L.S., Bartelt, A., Nilsson, S.K., Annaert, W., Christoffersen, C., Nielsen, L.B., Heeren, J., Roebroek, A.J.M.
PLos One 7:e38330, 2012, doi: 10.1371/journal.pone.0038330.

“GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries.”
Davies, B.S.J., Beigneux, A.P., Barnes, R.H., Tu, Y., Gin, P., Weinstein, M.M., Nobumori, C., Nyrén, R., Goldberg, I., Olivecrona, G., Bensadoun, A., Young, S.G., Fong, L.G.
Cell Metabolism, 12:42-52, 2010, doi: 10.1016/j.cmet.2010.04.016.

“Site-directed mutagenesis of apolipoprotein CII to probe the role of the secondary structure for activation of lipoprotein lipase.”
Shen, Y., Lookene, A., Zhang, L., Olivecrona, G.,
Journal of Biological Chemistry, 285:7484-7492, 2010, doi: 10.1074/jbc.M109.022046.

“Mutation of conserved cysteines in the Ly6 domain of GPIHBP1 in familial chylomicronemia”.
Olivecrona, G., Ehrenborg, E., Semb, H., Makoveichuk, E., Lindberg, A., Hayden, M.R., Gin, P., Davies, B.S.J., Weinstein, M.M., Fong, L.G., Beigneux, A.P., Young, S.G., Olivecrona, T., and Hernell, O,
Journal of Lipid Research 1535-1545, 2010, doi: 10.1194/jlr.M002717.

“Endocytosis of apolipoprotein AV by members of the low density lipoprotein receptor and the Vps10p domain receptor families”.
Nilsson, S.K., Christensen, S., Raarup, M.K., Ryan, R.O., Nielsen, M.S., Olivecrona G.
Journal of Biological Chemistry, 283:25920-25927, 2008, doi: 10.1074/jbc.m802721200.

“Effects of Six APOA5 Variants, Identified in Patients With Severe Hypertriglyceridemia, on In Vitro Lipoprotein Lipase Activity and Receptor Binding“.
Dorfmeister, B., Zeng, W.W., Dichlberger, A., Nilsson, S.K., Schaap, F.G., Hubacek, J.Lookene, A., Putt, W., Whittall, R., Lee, P.J., Lins. L., Delsaux, N., Nierman, M., Kuivenhoven, J.A., Kastelein, J.J., Vrablik, M., Olivecrona, G., Schneider, W.J., Heeren, J., Humphries, S.E., Talmud, P.J.
Arteriosclerosis, Thrombosis, Vascular Biology 28:1866-1871, 2008, doi: 10.1161/ATVBAHA.108.172866.

“Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family”.
Nilsson, S.K., Lookene, A., Beckstead, J.A., Gliemann, J., Ryan, R.O., Olivecrona, G.
Biochemistry 46:3896-3904, 2007, doi: 10.1021/bi7000533.

“Angiopoietin-like protein 4 converts lipoprotein lipase to inactive monomers and modulates lipase activity in adipose tissue”.
Sukonina, V., Looekene, A., Olivecrona, T., Olivecrona, G.
PNAS USA In press, 2006, doi: 10.1073/pnas.0604026103.

“Role of lipoprotein lipase in lipid metabolism”.
Olivecrona, G.
Current Opinion in Lipidology, 27:233-241, 2016, doi: 10.1097/MOL.0000000000000297.

“Apolipoprotein A-V; a potent triglyceride reducer”.  
Nilsson, S.K., Heeren, J., Olivecrona G., Merkel, M.
Atherosclerosis. 219:15-21, 2011, doi: 10.1016/j.atherosclerosis.2011.07.019.