Division of BioTherapeutics
Cardiovascular and Metabolic Therapeutics
This research group, headed by Miranda van Eck, focusses on understanding the molecular mechanisms underlying cardiovascular and metabolic diseases. Cardiovascular disease constitutes a major health issue worldwide. Although significant knowledge has been obtained on the development of atherosclerotic lesions and disturbances in lipid metabolism that underlies cardiovascular disease pathology, current treatments are only able to stop the progression of the disease, reducing mortality by only 25-30%. The overall ambition of the group of Van Eck is to identify novel targets for intervention in cardiovascular and metabolic disease and develop novel therapeutic strategies directly targeting macrophages in atherosclerotic lesions and improving lipid metabolism.
Miranda van Eck studied Bio-Pharmaceutical Sciences, specializing in Biopharmaceutics at the University of Leiden in The Netherlands. After her graduation in 1994 she obtained her PhD from Leiden University in 1999 on the use of the bone marrow transplantation technique as a novel strategy to study the role of macrophage genes in lipoprotein metabolism and atherogenesis. She is an expert in HDL metabolism and reverse cholesterol transport from the arterial wall to the liver and the role of ABC-transporters and scavenger receptor BI in this process. Her current research has extended to the identification of the role of novel genes in atherosclerotic lesion development, regression of atherosclerosis, and processes underlying the development of atherothrombosis.
Van Eck has over 120 publications in major international peer-reviewed scientific journals, that are frequently cited, indicating a wide international recognition. The h-index, an index that measures both the scientific productivity and the apparent scientific impact, for her publications is >40. Apart from attracting many citations, her work has led to a great number of international collaborations with consequently collaborative publications and invitations for key lectures at international meetings, including Gordon Conferences. Furthermore, it has led to several successful grant applications, including highly competitive VIDI (2005) and VICI (2013) Innovational Research grants from the Netherlands Organization for Scientific Research. Van Eck has received several prestigious awards, including the Galenus Research Prize which recognizes innovative pharmaceutical research in the Netherlands and twice an award from the International HDL Research Award Program for outstanding investigators in the field of HDL biology. Furthermore, since 2008, Van Eck is recognized as an Established Investigator by the Netherlands Heart Foundation. She is associate editor of “Atherosclerosis” and member of the editorial board of “Arteriosclerosis, Thrombosis, and Vascular Biology”.
Since 2012, Miranda van Eck is also acting member of the LACDR Board of Directors and Management Team. From 2012-2019, she was Programme Director of the Bachelor and Master programmes Bio-Pharmaceutical Sciences at Leiden University. As of September 2019 she is fully focussing on the Master programme Bio-Pharmaceutical Sciences as Programme Director.
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Research expertise and facilities
The research group of Miranda van Eck is specialized in experimental models of atherosclerosis and metabolic disease. There is long-standing expertise for studying macrophage function using amongst others the bone marrow transplantation techniques, as well as adrenal transplantation, and in vivo therapeutic intervention strategies. A wide array of techniques ranging from genomic analysis and in vitro cellular studies to advanced microscopy, histology, laser-capture microdissection and FACS analysis of tissues and cells are applied.
- Hoekstra M, Nahon JE, de Jong LM, Kröner MJ, de Leeuw LR, Van Eck M. Inhibition of PRMT3 activity reduces hepatic steatosis without altering atherosclerosis susceptibility in apoE knockout mice. Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1402-1409.
Ouweneel AB, Hoekstra M, van der Wel EJ, Schaftenaar FH, Snip OSC, Hassan J, Korporaal SJA, Van Eck M. Hypercholesterolemia impairs megakaryopoiesis and platelet production in scavenger receptor BI knockout mice. Atherosclerosis. 2019 Mar;282:176-182.
van der Sluis RJ, Verwilligen RAF, Lendvai Z, Wever R, Hoekstra M, Van Eck M. HDL is essential for atherosclerotic lesion regression in Apoe knockout mice by bone marrow Apoe reconstitution. Atherosclerosis. 2018 Nov;278:240-249.
Nahon JE, Hoekstra M, Havik SR, Van Santbrink PJ, Dallinga-Thie GM, Kuivenhoven JA, Geerling JJ, Van Eck M. Proteoglycan 4 regulates macrophage function without altering atherosclerotic lesion formation in a murine bone marrow-specific deletion model. Atherosclerosis. 2018 Jul;274:120-127.
Ouweneel A.B., Heestermans M., Verwilligen R.A., Gijbels M.J., Reitsma P.H., van Eck M., van Vlijmen B.J., Silencing of Anticoagulant Protein C Evokes Low Incident but Spontaneous Atherothrombosis in Apolipoprotein E-Deficient Mice. Arterioscler Thromb Vasc Biol. 2017 37(5): 782-785
- Louwe M.C., Lammers B., Frias M.A., Foks A.C., de Leeuw L.R., Hildebrand R.B., Kuiper J., Smit J.W.A., Van Berkel T.J.C., James R.W., Geerling J.J., Rensen P.C.N., Van Eck M., Abca1 deficiency protects the heart against myocardial infarction-induced injury. Atherosclerosis. 2016; 251: 159-163
- Hoekstra M., Van Eck M., HDL is redundant for adrenal steroidogenesis in LDLR knockout mice with a human-like lipoprotein profile. J Lipid Res. 2016; 57: 631-7
- van der Stoep M., Li Z., Calpe-Berdiel L., van der Sluis R.J., Saleh P., McKinnon H.J., Smit M.J., Korporaal S.J., Van Berkel T.J., Van Eck M., Hoekstra M., Elimination of macrophages drives LXR-induced regression both in initial and advanced stages of atherosclerotic lesion development. Biochem Pharmacol. 2013; 86: 1594-1602
- Korporaal S.J.A., Meurs I., Hauer A.D., Hildebrand R.B., Hoekstra M., Ten Cate H., Praticò D., Akkerman J.W.N., Van Berkel T.J.C., Kuiper J., Van Eck M., Deletion of the HDL receptor SR-BI in mice modulates thrombosis susceptibility and indirectly affects platelet function by elevation of plasma free cholesterol. Arterioscler Thromb Vasc Biol. 2011; 31: 34-42.
- Vergeer M., Korporaal S.J.A., Franssen R., Meurs I., Out R., Hovingh G.K., Hoekstra M., Sierts J.A., Dallinga-Thie G.M., Motazacker M.M., Holleboom A.G., Van Berkel T.J.C., Kastelein J.J.P., Van Eck M., Kuivenhoven J.A., A Genetic Variant of the Scavenger Receptor BI in Humans. N Engl J Med. 2011; 364: 136-145
- Zhao Y., Pennings M., Hildebrand R.B., Ye D., Calpe-Berdiel L., Out R., Kjerrulf M., Hurt-Camejo E., Groen A.K., Hoekstra M., Jessup W., Chimini G., Van Berkel T.J., Van Eck M., Enhanced foam cell formation, atherosclerotic lesion development, and inflammation by combined deletion of ABCA1 and SR-BI in Bone marrow-derived cells in LDL receptor knockout mice on western-type diet. Circ Res. 2010; 107: e20-e31
- Out R., Jessup W., Le Goff W., Hoekstra M., Gelissen I.C., Zhao Y., Kritharides L., Chimini G., Kuiper J., Chapman M.J., Huby T., Van Berkel T.J.C., Van Eck M., Coexistence of foam cells and hypocholesterolemia in mice lacking ABC transporters A1 and G1. Circ Res. 2008; 102: 113-120.
- Van Eck M., Bos I.S.T., Kaminski W.E., Orsó E., Rothe G., Twisk J., Böttcher A., Van Amersfoort E.S., Christiansen-Weber T.A., Fung-Leung W.-P., Van Berkel Th.J.C., Schmitz G., Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. Proc Nat Acad Sci USA. 2002; 99: 6298-303.