Novel mechanisms of atherosclerotic plaque (in)stability governed by smooth muscle cells


Translational Vascular Medicine lead by Ljubica Matic is a translational Team composed of basic researchers with expertise in molecular biology and pharmacology, and clinically active physicians. The Team applies integrative analyses combining bioinformatic and clinical data studies with murine models of vascular injury and disease, while in vitro systems based on primary cells and tissue explants are utilized for functional and mechanistic investigations.

Vascular diseases comprise conditions like atherosclerosis, aortic aneurysms and restenosis after surgical interventions, contributing to the high overall cardiovascular mortality. Pathological vessel changes are generally featured by inflammatory, apoptotic and remodeling processes involving lipids, immune and smooth muscle cells (SMCs). Given the capacity of SMCs to provide tissue integrity, we hypothesize that understanding of mechanisms that regulate their function can yield new strategies to prevent vascular complications. Therefore, we focus on novel molecular mechanisms of vascular disease particularly related to SMCs, as well as on biomarkers and therapeutic approaches in atherosclerosis.

Our ultimate goal is to develop new targets for stabilizing therapies or diagnostic imaging modalities aimed at early detection of vulnerable atherosclerotic plaques and patients. Our dedication to translational research in this area, as well as long-term collaborations with numerous groups worldwide (Stanford, Maastricht University, King’s College, Ottawa Heart Institute, Munich Technical University, etc.), have already demonstrated how a combination of clinical and experimental research has the true potential to advance the knowledge of vascular disease and improve patient management. 


Ljubica Matic

Ljubica Matic is an Associate Professor in Molecular Medicine at Karolinska Institutet. She obtained a PhD degree in Medical Biochemistry from Karolinska Institute, Sweden in 2012, and a MSc degree (Cum Laude) in Molecular Biology from Belgrade University, Serbia in 2003. Since 2012 she works in the Vascular Surgery Unit at Karolinska Institute, currently as Senior Researcher and Team Leader for Translational Vascular Medicine.

Ljubica Matic coordinates one of the largest human cohorts related to carotid atherosclerosis, the Biobank of Karolinska Endarterectomies (BiKE). Since 2020 she is also the Scientific Lead and co-founder for the KI-Novo Nordisk Cardiovascular Program (Joint Steering Board member). As investigator and supervisor, she participated in several EU FP7 and Horizon 2020 projects, i.e. CarTarDis, INTRICARE, CaReCyAn, etc. Her research has been distinguished with important national and international awards and fellowships, e.g. from the Sven and Ebba Hagberg Foundation, Swedish Research Council, Swedish Society for Medical Research, Swedish Heart-Lung Foundation and American Heart Association.

Since 2004, she has also been continuously devoted to pedagogical work as a mentor, lecturer, supervisor and Course Leader for undergraduate MSc and MD students in the Medicine and Biomedicine, as well as for PhD students in the Cardiovascular Program at KI.

Ljubica Matic has authored 70 articles with about 2000 citations, H-factor 23 and an average JIF 9.3. She acts as reviewer for several EU national research foundations (Austria, Poland, the Netherlands) and numerous journals, such as Atherosclerosis, Eur J Vasc and Endovasc Sur, J Vasc Sur, Cardiovasc Res, FASEB, Frontiers in Cardiovasc Med, Am J Hum Genet, ACS Nano, etc.


Selected Publications

Perisic L*#, Aldi S*, Sun Y, Folkersen L, Razuvaev A, Roy J, Lengquist M, Åkesson S, Wheelock CE, Maegdefessel L, Gabrielsen A, Odeberg J, Hansson GK, Paulsson-Berne G, Hedin U. Gene expression signatures, pathways and networks in carotid atherosclerosis. J Intern Med 2016, Mar;279(3):293-308 .

(#corresponding author, * equal contribution)


Perisic L*, Hedin E, Razuvaev A, Lengquist M, Osterholm C, Folkersen L, Gillgren P, Paulsson-Berne G, Ponten F, Odeberg J, Hedin U. Profiling of atherosclerotic lesions by gene and tissue microarrays reveals PCSK6 as a novel protease in unstable carotid atherosclerosis. Arterioscler Thromb Vasc Biol 2013. *corresponding author

Rykaczewska U*, Suur BE*, Röhl S*, Razuvaev A, Lengquist M, Sabater-Lleal M, van der Laan SW, Miller CL, Wirka RC, Kronqvist M, Gonzalez Diez M, Vesterlund M, Gillgren P, Odeberg J, Lindeman JH, Veglia F, Humphries SE de Faire U, Baldassarre D Tremoli E, Lehtiö J, Hansson GK, Paulsson-Berne G, Pasterkamp G, Quertermous T, Hamsten A, Eriksson P, Hedin U#, Matic L#§. PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling. Circ Res. 2020 Feb 2020 (*,# equal contribution, § corresponding author)

Perisic Matic L*, Rykaczewska U, Razuvaev A, Sabater-Lleal M, Lengquist M, Miller CL, Ericsson I, Röhl S, Kronqvist M, Aldi S, Magné J, Paloschi V, Vesterlund M, Li Y, Jin H, Gonzalez Diez M, Roy J, Baldassarre D, Veglia F, Humphries SE, de Faire U, Tremoli E, on behalf of the IMPROVE study group, Odeberg J, Vukojević V, Lehtiö J, Maegdefessel L, Ehrenborg E, Paulsson-Berne G, Hansson GK, Lindeman JHN, Eriksson P, Quertermous T, Hamsten A, Hedin U. Phenotypic modulation of smooth muscle cells in atherosclerosis is associated with downregulation of LMOD1, SYNPO2, PDLIM7, PLN and SYNM. Arterioscler Thromb Vasc Biol 2016. *corresponding author

Matic Perisic Ljubica*, Iglesias Maria Jesus*, Vesterlund Mattias, Lengquist Mariette, Hong Mun-Gwan, Razuvaev Anton, Roy Joy, Berg Martin, Persson Jonas, Kronqvist Malin, Gillgren Peter, Lehtiö Janne, Paulsson-Berne Gabrielle, Hansson K Göran, Odeberg Jacob# and Hedin Ulf#. Combination of plasma proteomics with plaque transcriptomics reveals BLVRB as a candidate marker of carotid atherosclerosis. JACC: Basic to Transl Sci 2018. (*,# equal contribution)

Röhl S*, Rykaczewska U*,  Seime T*, Suur BE, Gonzalez Diez M, Gådin JR, Gainullina A, Sergushichev AA, Wirka R, Lengquist M, Kronqvist M, Bergman O, Odeberg J, Lindeman JHN, Quertermous T, Hamsten A, Eriksson P, Hedin U, Razuvaev A#, Matic L#,§. Transcriptomic profiling of experimental arterial injury reveals new mechanisms and temporal dynamics in vascular healing response.

J Vasc Surgery-Vasc Sci. In press

(*,# equal contribution, § corresponding author).

Yoko Kojima, Jens-Peter Volkmer, Kelly McKenna, Mete Civelek, A. Jake Lusis, Clint Miller, Daniel Direnzo, Vivek Nanda, Shannon Brady, Andrew Connolly, Eric Schadt, Thomas Quertermous, Paola Betancur, Lars Maegdefessel, Ljubica Perisic Matic, Ulf Hedin, Irving Weissman and Nicholas J Leeper. CD47 blocking antibodies restore phagocytosis and prevent atherosclerosis. 

Nature 2016, Aug 4;536(7614):86-90.

Hovsep Mahdessian*, Ljubica Perisic Matic*, Mariette Lengquist, Karl Gertow, Bengt Sennblad, Damiano Baldassarre, Fabrizio Veglia, Steve E. Humphries, Rainer Rauramaa, Ulf de Faire, Andries J. Smit, Philippe Giral, Sudhir Kurl, Elmo Mannarino and Elena Tremoli, on behalf of the IMPROVE study group, Anders Hamsten, Per Eriksson, Ulf Hedin#, Anders Mälarstig#. Integrative Studies Implicate Matrix Metalloproteinase 12 as a Culprit Gene for Large-Artery Atherosclerotic Stroke. J Intern Med 2017. *, # equal contribution

Konstantinos Stellos, Aikaterini Gatsiou, Kimon Stamatelopoulos, Ljubica Perisic Matic, David John, Federica Francesca Lunella, Nicolas Jaé, Oliver Rossbach, Carolin Amrhein, Frangiska Sigala, Reinier A. Boon, Boris Fürtig, Yosif Manavski, Xintian You, Shizuka Uchida, Till Keller, Jes-Niels Boeckel, Lars Maegdefessel, Wei Chen, Harald Schwalbe, Albrecht Bindereif, Per Eriksson, Ulf Hedin, Andreas M. Zeiher, Stefanie Dimmeler. Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation. Nat Med. 2016 Oct;22(10):1140-1150.

Gallina AL, Rykaczewska U, Wirka RC, Caravaca AS, Shavva VS, Youness M, Karadimou G, Lengquist M, Razuvaev A, Paulsson-Berne G, Quertermous T, Gisterå A, Malin SG, Tarnawski L, Matic L*, Olofsson PS*. AMPA-Type Glutamate Receptors Associated With Vascular Smooth Muscle Cell Subpopulations in Atherosclerosis and Vascular Injury. Frontiers in Cardiovasc Med 2021. (*equal contribution)

Buckler AJ, Karlöf E, Lengquist M, Gasser TC, Maegdefessel L, Perisic Matic L, Hedin U. Virtual Transcriptomics: Noninvasive Phenotyping of Atherosclerosis by Decoding Plaque Biology From Computed Tomography Angiography Imaging. Arterioscler Thromb Vasc Biol 2021.

Samuel Röhl, Bianca E. Suur, Mariette Lengquist, Till Seime, Kenneth Caidahl, Ulf Hedin, Anders Arner, Ljubica Matic* and Anton Razuvaev*. Lack of PCSK6 Increases Flow-Mediated Outward Arterial Remodeling in Mice. Cells 2020. (*equal contribution and shared corresponding authors).

Till Seime, Asim Cengiz Akbulut, Moritz Lindquist Liljeqvist, Antti Siika, Hong Jin, Greg Winski, Rick H van Gorp, Eva Karlöf, Mariette Lengquist, Andrew J Buckler, Malin Kronqvist, Olivia J Waring, Jan H N Lindeman, Erik A L Biessen, 

Lars Maegdefessel, Anton Razuvaev, Leon J Schurgers, Ulf Hedin, Ljubica Matic. Proteoglycan 4 Modulates Osteogenic Smooth Muscle Cell Differentiation during Vascular Remodeling and Intimal Calcification

Cells, 2021 May 21;10(6):1276.

Han Jin, Pieter Goossens, Peter Juhasz, Wouter Eijgelaar, Marco Manca, Joël M H Karel, Evgueni Smirnov, Cornelis J J M Sikkink, Barend M E Mees, Olivia Waring, Kim van Kuijk, Gregorio E Fazzi, Marion J J Gijbels, Martina Kutmon, Chris T A Evelo, Ulf Hedin, Mat J A P Daemen, Judith C Sluimer, Ljubica Matic, Erik A L Biessen. Integrative multiomics analysis of human atherosclerosis reveals a serum response factor-driven network associated with intraplaque hemorrhage.

Clin Transl Med 2021 Jun;11(6):e458.

Eva Karlöf, Till Seime, Nuno Dias, Mariette Lengquist, Malin Kronqvist, Jesper R Gådin, Håkan Almqvist, Odeberg Jacob, Anna Witasp, Peter Stenvinkel, Lars Maegdefessel, Ljubica Perisic Matic*, Ulf Hedin*. Correlation of Preoperative Computer Tomography with Carotid Plaque Gene Expression Profiles Demonstrates an Association Between Calcification and Plaque-Stabilizing Processes. Atherosclerosis 2019 

(*equal contribution and corresponding authors)