Experimental Research of the Department of Vascular Surgery

Experimental research of the Department of Vascular Surgery (Experimental Vascular Surgery) is located at the Campus Schlieren of the USZ/UZH. Even if our scientific work is devoted the basic research, it is still clinically oriented, with the aim of translational research endeavouring to implement the achieved results into the clinical everyday life.

The main research areas are the exploration of molecular-biological processes leading to substantial changes in atherosclerotic lesions of the vessel wall of peripheral arteries and aortic aneurysm, affected in particular by age. The aim is to create a profound basis to improve existing diagnostic and therapeutic measures for personalised medicine. In order to engage in profound translational research, human vascular tissue samples from patients with cardiovascular diseases are necessary. Hence, the particular focus of our research is the establishment and expansion of our SWISS VASCULAR BIOBANK (SVB), collecting tissue samples from patients suffering from high-grade carotid stenosis (CAS), aortic aneurysm (AA) and peripheral artery disease (PAD), who underwent surgical intervention in our department.

In spite of intensive research, the underlying pathophysiological mechanisms leading to formation and progression of atherosclerosis, in particular biological processes and factors causing vulnerable atherosclerotic plaques, and in case of CAS frequently ischemic stroke, are still unsolved. The same applies also to aortic aneurysm, in particular AAA, which proceeds mainly asymptomatic and in case of rupture results frequently in death of the affected person.

Therefore, personalise and reliable prognosis of vulnerable atherosclerotic plaques or rupture-prone aneurysms is of outstanding importance and the aim of our ongoing research.

Regarding methodology, our research group is employing the state-of-the-art techniques such as proteome and transcriptome analyses, RNA and single-cell sequencing, exploration of epigenetic changes such as DNA methylation, histone methylation and acetylation, expression of non-coding RNAs. Moreover, the standard molecular-biological methods such as immunohistochemistry, qRT-PCR, western blotting and ELISA assays are applied as well.

Research topics

Contact

If you are interested in our research, please, contact:

 

Jaroslav Pelisek, Prof. Dr. rer. nat.
Head Experimental Vascular Surgery
University Hospital Zurich, USZ
Department of Vascular Surgery
Wagistrasse 2
8952 Schlieren

Tel. +41 43 253 13 20

Our projects

  • Swiss Vascular Biobank (BASEC-Nr. 2020-00378)
    Collection of vascular tissue from patients, who undergo surgical intervention in our Department of Vascular Surgery or cooperation departments:
  • Thoracic and abdominal aortic aneurysm (TAA, AAA)
  • Aneurysm of iliac or popliteal arteries (IA, PA)
  • Aortic Arch (AB = Aortenbogen) (Department of Heart Surgery)
  • Carotid plaques (Carotid Artery Stenosis, CAS)
  • Peripheral artery Disease (PAK)
  • Non-aneurysmal aortic wall following kidney transplantation (Department of Visceral- and Transplantation Surgery)
  • Deutsche Forschungsgemeinschaft (DFG) (2017-2021): Individualisierte Rupturrisikostratifizierung und Analyse mechanobiologischer Interaktionen beim abdominalen Aortenaneurysma
  • Deutsche Forschungsgemeinschaft (DFG) (2017-2021): Epigenetische Veränderungen in atherosklerotischen Läsionen hirnversorgender Arterien: Relevanz für das Risiko des ischämischen Schlaganfalls?

  • NRP 78 “Covid-19”: The role of COVID-19 in cardiovascular disease (CVD): Impact on endothelial and smooth muscle cells derived from patients with aortic and peripheral arterial diseases using self-made SARS-CoV-2 pseudovirus
  • SNF: Lead Agency mit Tschechien: Proteome and transcriptome analysis of human elective versus ruptured abdominal aortic aneurysm for personalized medicine
  • SPARK: Molecular nature of baroreceptors in human aortic arch

Publications

  • Pelisek J, Hegenloh R, Bauer S, Metschl S, Pauli J, Glukha N, Busch A, Reutersberg B, Kallmayer M, Trenner M, Wendorff H, Tsantilas P, Schmid S, Knappich C, Schaeffer C, Stadlbauer T, Biro G, Wertern U, Meisner F, Stoklasa K, Menges AL, Radu O, Dallmann-Sieber S, Karlas A, Knipfer E, Reeps C, Zimmermann A, Maegdefessel L, Eckstein HH.Biobanking: objectives, requirements and future challenges – experiences from the Munich Vascular Biobank. J Clin Med. 2019;8(2). pii: E251.
  • Reutersberg B, Peters A, Hakimi M, Pelisek J, Eckstein HH, Jahns R, Busch A. Die Vaskuläre Biobank – hands on. Gefässchirurgie. 2018;23(3):185-188.
  • Wendorff C, Wendorff H, Kuehnl A, Tsantilas P, Kallmayer M, Eckstein HH, Pelisek J. C Impact of sex and age on carotid plaque instability in asymptomatic patients – Results from the Munich Vascular Biobank – VASA, 2016;45(5):411-416.
  • Wendorff C, Wendorff H, Pelisek J, Tsantilas P, Zimmermann A, Zernecke A, Kuehnl A, Eckstein HH. Carotid plaque morphology is significantly associated with sex, age and history of neurological symptoms – Results from the Munich Vascular Biobank – Stroke. 2015;46(11):3213-9.

  • Xu S, Xu Y, Liu P, Zhang S, Liu H, Slavin S, Kumar S, Koroleva M, Luo J, Wu X, Rahman A, Pelisek J, Jo H, Si S, Miller CL, Jin ZG. The novel coronary artery disease risk gene JCAD/KIAA1462 promotes endothelial dysfunction and atherosclerosis. Eur Heart J. 2019;25(3):529.
  • Bianchini M, Duchêne J, Santovito D, Schloss MJ, Evrard M, Winkels H, Aslani M, Mohanta SK, Horckmans M, Blanchet X, Lacy M, von Hundelshausen P, Atzler D, Habenicht A, Gerdes N, Pelisek J, Ng LG, Steffens S, Weber C, Megens RTA. PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function. Sci Immunol. 2019;4(36).pii: eaar305.
  • Yin C, Ackermann S, Ma Z, Mohanta SK, Li Y, Nietzsche S, Westermann M, Peng L, Hu D, Bontha SV, Srikakulapu P, Beer M, Megens RTA, Steffens S, Hildner M, Eckstein HH, Pelisek J, Herms J, Arzberger T, Habenicht L, Binder C, Weber C, Zipfel PF, Skerka C, Habenicht AJR. ApoE attenuates unresolvable inflammation by complex formation with activated C1q. Nat Med. 2019;25(3):496-506.
  • Cochain C, Vafadarnejad E, Arampatzi P, Pelisek J, Holger C, Klaus D, Wolf D, Saliba AE, Zernecke A. Single-cell RNA-seq reveals the transcriptional landscape and heterogeneity of aortic macrophages in murine atherosclerosis. Circ Res. 2018;122(12):1661-1674.
  • Jin H, Li DY, Chernogubova E, Sun C, Busch A, Eken SM, Saliba-Gustafsson P, Winter H, Winski G, Raaz U, Schellinger IN, Simon N, Hegenloh R, Matic LP, Jagodic M, Ehrenborg E, Pelisek J, Eckstein HH, Hedin U, Backlund A, Maegdefessel L. Local Delivery of miR-21 Stabilizes Fibrous Caps in Vulnerable Atherosclerotic Lesions. Mol Ther. 2018;26(4):1040-1055.
  • Merckelbach S, van der Vorst EPC, Kallmayer M, Rischpler C, Burgkart R, Döring Y, de Borst GJ, Schwaiger M, Eckstein HH, Weber C, Pelisek J. Expression and Cellular Localization of CXCR4 and CXCL12 in Human Carotid Atherosclerotic Plaques. Thromb Haemost. 2018;118(1):195-206.
  • Pelisek J, Deutsch L, Ansel A, Rudelius M, Pongratz J, Stadlbauer T, Gebhard H, Eckstein HH. Expression of a metalloproteinase family of ADAMTS in human vulnerable carotid lesions: implication for clinical practice. J Cardiovasc Med. 2017;18(1):10-18.
  • Eken SM, Jin H, Chernogubova E, Li Y, Simon N, Sun C, Korzunowicz G, Busch A, Bäcklund A, Österholm C, Razuvaev A, Renné T, Eckstein HH, Pelisek J, Eriksson P, Gonzalez Diez M, Matic Perisic LP, Schellinger IN, Raaz U, Leeper NJ, Hansson GK, Paulsson-Berne G, Hedin U, Maegdefessel L. MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions. Circ Res. 2017;120(4):633-644.
  • Hyafil F, Pelisek J, Laitinen I, Schottelius M, Mohring M, Döring Y, Van der Vorst E, Kallmayer M, Steiger K, Poschenrieder A, Notni J, Fischer J, Baumgartner C, Rischpler C, Nekolla S, Weber C, Eckstein HH, Wester HJ, Schwaiger M. Imaging the cytokine receptor CXCR4 in atherosclerotic plaques with the radiotracer 68Ga-pentixafor for positron emission tomography. J Nucl Med. 2017;58(3):499-506.
  • Glinzer A, Ma X, Prakash J, Kimm MA, Lohöfer F, Kosanke K, Pelisek J, Thon MP, Vorlova S, Heinze KG, Eckstein HH, Gee MW, Nitziachristos V, Zernecke A, Wildgruber M. Targeting Elastase for Molecular Imaging of Early Atherosclerotic Lesions. Arterioscler Thromb Vasc Biol. 2017;37:525-533.
  • Pelisek J, Wendorff C, Wendorff H, Kuehnl A, Eckstein HH. Age-associated changes in human carotid atherosclerotic plaques. Annals of Med. 2016;48(7):541-551.
  • Seeger M, Karlas A, Soliman D, Pelisek J, Ntziachristos V. Multimodal optoacoustic and multiphoton microscopy of human carotid atheroma. Photoacoustics, 2016;4(3):102-111.
  • Boeckh-Behrens T, Schubert MI, Förschler A, Prothmann S, Kreiser K, Zimmer C, Riegger J, Bauer J, Neff F, Kehl V, Pelisek J, Schirmer L, Mehr M, Poppert H. The Impact of Histological Clot Composition in Embolic Stroke. Clin Neuroradiol. 2016;26(2):189-197.
  • Boeckh-Behrens T, Kleine JF, Zimmer C, Neff F, Scheipl F, Pelisek J, Schirmer L, Nguyen K, Karatas D, Poppert H. Thrombus histology suggests cardio-embolic etiology in cryptogenic stroke. Stroke, 2016;47(7): 1864-1871.
  • Cochain C, Koch M, Chaudhari SM, Busch M, Pelisek J, Boon L, Zernecke A. CD8+ T Cells Regulate Monopoiesis and Circulating Ly6Chigh Monocyte Levels in Atherosclerosis in Mice. Circ Res. 2015; 117(3):244-53.
  • Chaudhari S, Sluimer J, Koch M, Theelen T, Manthey H, Busch M, Caballero-Franco C, Cochain C, Pelisek J, Daemen M, Lutz M, Gorlach A, Kissler S, Hermanns H, Zernecke A. Deficiency of HIF1alpha in antigen-presenting cells aggravates atherosclerosis and type 1 T helper cell responses in mice. Arterioscler Thromb Vasc Biol. 2015;35(11):2316-2325.
  • Beer AJ, Pelisek J, Heider P, Saraste A, Reeps C, Metz S, Seidl S, Kessler H, Hans- Wester J, Eckstein HH, Schwaiger M. In-vivo PET/CT imaging of integrin αvß3 expression in human carotid plaques as a biomarker of inflammatory atherosclerotic lesions. JACC-Cardiovasc Imaging. 2014;7:178-187.
  • Chmielewski S, Olejnik A, Sikorski K, Pelisek J, Zernecke A, Heemann U, Wesoly J, Baumann M, Bluyssen H. STAT1 and IRF8 orchestrate IFN and LPS-mediated signal integration in the vasculature that leads to amplified pro-atherogenic responses. PLoS One, 2014;9(12):e113318.
  • Manthey HD, Cochain C, Barnsteiner S, Karshovska E, Pelisek J, Koch M, Chaudhari SM, Busch M, Eckstein HH, Weber C, Koenen RR, Zernecke A. CCR6 selectively promotes monocyte mediated inflammation and atherogenesis in mice. Thromb Haemost. 2013;110(6):1267-77.
  • Pelisek J, Pongratz J, Deutsch L, Reeps C, Stadlbauer T, Eckstein HH. Expression and cellular localisation of metalloproteases ADAMs in high graded car. artery lesions. Scand J Clin Lab Invest. 2012;72:648-656.
  • Pelisek J, Reeps C, Ockert S, Zimmermann A, Zepper P, Poppert H, Eckstein HH. Evaluation of serum biomarkers for patients at increased risk of stroke. Int J Vasc Med. 2012:906954.
  • Döring Y, Manthey H, Drechsler M, Megens R, Lievens D, Manca M, Busch M, Koenen RR, Soehnlein O, Pelisek J, Zenke M, Daemen MJ, Weber C, Lutgens E, Zernecke A. Autoantigenic protein-DNA complexes stimulate plasmacytoid dendritic cells to promote atherosclerosis. Circulation. 2012;125(13):1673-1683.
  • Pelisek J, Well G, Reeps C, Poppert H, Kuehnl A, Baumann M, Heemann U, Eckstein HH. Neovascularisation and angiogenic factors in advanced human carotid artery stenosis. Circulation J. 2012;76(5):1274-1282.
  • Stolla M. Pelisek J, von Brühl, ML, Schäfer A, Heider P, Barocke V, Lorenz M, Tirniceriu A, Steinhart A, Bauersachs J, Bray PF, Massberg S, Schulz C. Fractalkine is Expressed in Early and Advanced Atherosclerotic Lesions and Directly Supports Monocyte Recruitment via CX3CR1. PLoS ONE, 2012;7(8):e43572.
  • Heider P, Pelisek J, Poppert H, Eckstein HH. Evaluation of serum matrix metalloproteinases and serological factors as biomarkers for detection of neurological symptoms. Vasc Endovasc Surg. 2009;43(6):551-60.
  • Pelisek J, Rudelius M, Zepper P, Schuster T, Seidl S, Reeps C, Zimmermann A, Poppert H, Eckstein HH. Multiple biological predictors for vulnerable carotid lesions. Cerebrovasc Diseases. 2009;28(6):601-610.

  • Kojima Y, Werner N, Ye J, Nanda V, Tsao N, Wang Y, Flores AM, Miller CL, Weissman I, Deng H, Xu B, Dalman RL, Eken SM, Pelisek J, Li Y, Maegdefessel L, Leeper NJ. Proefferocytic Therapy Promotes Transforming Growth Factor-β Signaling and Prevents Aneurysm Formation. 2018;137(7):750-753.
  • Klaus V, Tanios-Schmies F, Reeps C, Trenner M, Geisbüsch S, Lohoefer F, Eckstein HH, Pelisek J. Cathepsin B and S are associated with the degraded product of collagen I in abdominal aortic aneurysm VASA. 2018;47(4):285-293.
  • Biehler J, Kehl S, Gee MW, Tanios F, Pelisek J, Maier A, Reeps C, Eckstein HH, Wall WA. Probabilistic Non-Invasive Prediction of Wall Properties of Abdominal Aortic Aneurysms Using Bayesian Regression Biomech Model Mechan. 2017;16(1):45-61.
  • Klaus V, Tanios-Schmies F, Reeps C, Trenner M, Matevossian E, Eckstein HH, Pelisek J. Association of MMP levels with collagen degradation in the context of AAA. Eur J Vasc Endovasc Sur. 2017;53:549-558.
  • Tanios F, Pelisek J, Lutz B, Reutersberg B, Kallmayer M, Matevossian E, Schwamborn K, Hösel V, Eckstein HH, Reeps C. CXCR4: a potential marker for inflammatory activity in abdominal aortic aneurysm wall. Eur J Vasc Endovasc Sur. 2015;50(6):745-753.
  • Tanios F, Gee MW, Pelisek J, Kehl S, Biehler J, Haneder S, Grabher-Meier V, Wall WA, Eckstein HH. Reeps C. Interaction of biomechanics with extracellular matrix components in abdominal aortic aneurysm wall. Eur J Vasc Endovasc Surg. 2015;50(2):167-174.
  • Lohoefer F, Reeps C, Lipp C, Rudelius M, Haertl M, Eckstein HH, Pelisek J. Quantitative expression and localisation of cysteine proteases in human abdominal aortic aneurysm. Exp Mol Med. 2014;9(6):e90846.
  • Reeps C, Kehl S, Tanios F, Biehler J, Pelisek J, Maier A, Wall WA, Eckstein HH, Gee MW. Biomechanics and gene expression in abdominal aortic aneurysm. J Vasc Surg, 2014;60(6):1640-1647.e2.
  • Reeps A, Maier A, Pelisek J, Härtl F, Grabher-Meier V, Wall WA, Essler M, Eckstein HH, Gee M. Measuring and Modeling the Patient-Specific Distributions of Material Properties in Abdominal Aortic Aneurysm Wall. Biomech Model Mechanobiol, 2013;12(4):717-733.
  • Reeps C, Bundschuh RA, Pelisek J, Herz M, van Marwick S, Schweiger M, Eckstein HH, Nekolla SG, Essler M. (2013) Quantitative assessment of glucose metabolism in the vessel wall of abdominal aortic aneurysms: correlation with histology and role of partial volume correction. Int J Cardiovasc Imaging, 2013;29(2):505-512.
  • Lipp C, Lohoefer F, Reeps C, Rudelius M, Baumann M, Heemann U, Eckstein HH, Pelisek J. Expression of a disintegrin and metalloprotease family of proteins in human abdominal aortic aneurysms. J Vasc Res. 2012;49(3):198-206.
  • Lohoefer F, Reeps C, Lipp C, Rudelius M, Zimmermann A, Eckstein HH, Pelisek J. Histological analysis and localisation of cathepsins in human abdominal aortic aneurysm. Int J Exp Pathol, 2012;93(4):252-258.
  • Reeps C, Pelisek J, Seidl S, Schuster T, Zimmermann A, Wendorff H, Kuehnl A, Eckstein HH. Inflammatory infiltrates and neovessels are relevant sources of MMPs in abdominal aortic aneurysm wall. Pathobiology. 2009;76(5):243-252.
  • Reeps C, Gee MW, Maier A, Pelisek J, Gurdan M, Wall W, Mariss J, Eckstein HH, Essler M. Glucose Metabolism in the Vessel Wall Correlates With Mechanical Instability and Inflammatory Changes in a Patient With a Growing Aneurysm of the Abdominal Aorta. Circulation – Cardiovasc Imaging. 2009;2(6):507-509.

  • Xu S, Kamato D, Little PJ, Nakagawa S, Pelisek J, Jin ZG. Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics. Pharmacol Ther. 2019;196:15-43.
  • Xu S, Pelisek J, Jin ZG. Atherosclerosis is an epigenetic disease. Trends Endocrinol Metab. 2018;S1043-2760(18)30090-0.
  • Greißel A, Culmes M, Rudelius M, Burgkart R, Zernecke A, Eckstein HH, Pelisek J. (2015) Histone acetylation and methylation in high graded carotid plaques. Cardiovasc Pathol, 2016;25(2):79-86.
  • Culmes M, Greißel A, Napieralski R, Dushenalieva S, Wagner E, Gebhard H, Schmidt M, Eckstein HH, Zernecke A, Pelisek J. DNA methylation in carotid plaques is associated with severity of atherosclerosis and reduced expression of DNA methyltransferases. Thromb Haemost. 2015;21:114(2).
  • Yan X, Ehnert S, Culmes M, Claudine C, Schyschka L, Wang Z, Stöckle U, De Sousa PA, Pelisek J, Nussler AK. Small molecule epigenetic inhibitors improve osteogenic differentiation of aged human adipose-derived mesenchymal stem cells by DNA demethylation. PLoS One. 2014;i9(6):e90846.
  • Culmes M, Eckstein HH, Burgkart R, Nüssler AK, Guenther M, Wagner E, Pelisek J. Endothelial differentiation of Adipose derived mesenchymal stem cells is improved by BIX-01294, an epigenetic modifying drug. Eur J Cell Biol. 2013;92(2):70-79.
  • Pelisek J, Eckstein HH, Zernecke A. (2012) Pathophysiological mechanisms of carotid plaque vulnerability: impact on ischemic stroke. Arch Immunol Ther Exp. 2012;60(6):431-442.

  • He Y, Xing J, Wang S, Pelisek J, Jiang H, Xin S, Han Y, Zhang J. Increased m6A mRNA methylation levels are correlated with the progression of human abdominal aortic aneurysm. Epigenetics 2020; submitted.
  • Li DY, Busch A, Jin H, Chernogubova E, Pelisek J, Karlsson J, Sennblad B, Liu S, Lao S, Hofmann P, Bäcklund A, Eken SM, Roy J, Eriksson P, Dacken B, Ramanujam D, Dueck A, Engelhardt S, Boon RA, Eckstein HH, Spin JM, Tsao PS, Maegdefessel L. H19 Induces Abdominal Aortic Aneurysm Development and Progression. Circulation. 2018;138(15):1551-1568.
  • Xu S, Xu Y, Yin M, Zhang S, Liu P, Koroleva M, Si S, Little PJ, Pelisek J, Jin ZG. Flow-dependent epigenetic regulation of IGFBP5 by H3K27me3 contributes to endothelial anti-inflammatory effects. Theranostics. 2018;8(11):3007-3021.
  • Han Y, Tanios F, Reeps C, Zhang J, Schwamborn K, Lutz B, Eckstein HH, Zernecke A, Pelisek J. Histone acetylation and expression of corresponding histone acetyl-transferases in human abdominal aortic aneurysm. Clin Epigenetics. 2016; 8:3.