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Studies on the role of extracellular vesicles

Extracellular vesicles (exosomes, microvesicles) are players of intracellular communication. They have been known for some time now, but their role in numerous physiologic and pathologic processes has been proven only recently.

Figure 1: (a) Donor cells release extracellular vesicles (EVs), which contain different cargoes (lipids, proteins, RNA, DNA). (b) EVs are taken up by recipient cells, which can be through membrane fusion or receptor-mediated endocytosis. (Source: Szempruch et al., 2016)

Figure 2: Electronmicroscopic image of EVs from rat blood.

Our workgroup studies therapeutic opportunities of ischemic states of the heart (e.g., angina, infarction), including the possible use of EVs released during cardioprotective interventions and of their cargo miRNA and proteins. The aim of our studies is to develop novel therapeutic or diagnostic/prognostic tools for the treatment of ischemic heart diseases, which has a potential to be applied in the clinical setting.

Group leader: Dr Zoltán Giricz senior research associate (Google Scholar)

Publications in the field:

  • Onódi Z, Pelyhe C, Nagy CT, Brenner GB, Almási L, Kittel Á, Mancek Keber M, Ferdinandy P, Buzás EI and Giricz G. Isolation of high-purity extracellular vesicles by the combination of iodixanol density gradient ultracentrifugation and bind-elute chromatography from blood plasma. Front Physiol. 2018 Oct 23;9:1479. (link)
  • Sluijter JPG, Davidson SM, Boulanger CM, Buzás EI, de Kleijn DPV, Engel FB8, Giricz Z, Hausenloy DJ, Kishore R, Lecour S, Leor J, Madonna R, Perrino C, Prunier F, Sahoo S, Schiffelers RM, Schulz R, Van Laake LW, Ytrehus K, Ferdinandy P. Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res. 2018 Jan 1;114(1):19-34. (link)
  • Sódar BW, Kittel Á, Pálóczi K, Vukman KV, Osteikoetxea X, Szabó-Taylor K, Németh A, Sperlágh B, Baranyai T, Giricz Z, Wiener Z, Turiák L, Drahos L, Pállinger É, Vékey K, Ferdinandy P, Falus A, Buzás EI. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection. Sci Rep. 2016 Apr 18; 6:24316. (link)
  • Baranyai T, Herczeg K, Onodi Z, Voszka I, Modos K, Marton N, Nagy G, Mäger I, Wood MJ, El Andaloussi S, Palinkas Z, Kumar V, Nagy P, Kittel A, Buzas E, Ferdinandy P, Giricz Z. Isolation of Exosomes from Blood Plasma: Qualitative and Quantitative Comparison of Ultracentrifugation and Size Exclusion Chromatography Methods. PLoS One. 2015 Dec 21; 10 (12): e0145686. (link)
  • Giricz Z, Varga ZV, Baranyai T, Sipos P, Pálóczi K, Kittel Á, Buzás EI, Ferdinandy P. Cardioprotection by remote ischemic preconditioning of the rat heart is mediated by extracellular vesicles. J Mol Cell Cardiol. 2014 Mar;68:75-8. (link)

Achievements of undergrad researchers:

  • Laura Almási, Semmelweis University TDK Conference, Budapest, Hungary, 2019, 3rd prize
  • Bence Kenyeres, Semmelweis University TDK Conference, Budapest, Hungary, 2019, 3rd prize
  • Laura Almási, XXIII. Korányi Frigyes Tudományos Fórum, , Budapest, Hungary, 2018, 2nd prize
  • Zsófia Onódi, XXXIII. OTDK, Budapest, Hungary, 2017, 1st prize

Current projects:

Studying the role of EVs in cardioprotective interventions

We isolate and study EVs released from various primary cells and cell lines after cardioprotective interventions. We perform quantitative and qualitative analyses, and study their potential use in therapies against detrimental effects of simulated ischemia/reperfusion (sI/R) in various cell cultures.

Learning opportunities: cell culturing, performing viability assays, operating fluorescent microscope, data analysis and presentation

Project leader: Dr Csilla Pelyhe research associate, Dr Zoltán Giricz senior research associate

Studying the role of EVs in metabolic co-morbidities of cardiac diseases

The aim of the project is to study biophysical properties of EV membranes in metabolic diseases. Furthermore, we aim to study cardioprotective effects of EVs from the blood of animals with metabolic diseases in cell lines and rat primary cariac cells in sI/R. In this project we isolate EVs from the blood of animals with metabolic diseases such as diabetes, obesity, hyperlipidemia. We characterize these EVs and study their effect in sI/R in cellular models. The metabolic imbalance may influence the content and membrane composition of EVs. We measure membrane physical parameters, cell viability, gene expression, and thus we will analyze the activation of cardioprotective mechanisms.

Figure 3. After isolation of EVs In vivo their role in protection against sI/R is assessed in cellular models.

Learning opportunities: working with animals, EV isolation from blood, Western Blot, qPCR, cell culturing, viability tests, operating fluorescent microscope, measurement of biophysical parameters (AFM), ischemia/reperfusion in cells, data analysis and presentation.

Project leader: Dr Zoltán Giricz senior research associate

Studying the role of EVs in ischemic conditioning

In this project we study cardioprotective mechanisms in vitro by assessing biophysical and biochemical biological properties of EVs released after cardioprotective interventions in transgenic cellular models. We study effects of EVs on signaling pathways related to the inflammatory processes activated after ischemia/reperfusion injury. We also investigate EV dynamics during I/R injury. For these experiments, we utilize CRISPR/Cas9 gene technology and in-vivo and cellular imaging technologies.

Figure 4. Isolation of EVs labelled with fluorescent proteins, assessment of their biophysical properties, in vivo and in vitro tracking of EV dynamics.

Learning opportunities: cell culturing, operating fluorescent microscope, molecular biological works with plasmids and proteins, gene silencing (CRISPR/Cas9), establishing transgenic cell lines, data analysis and presentation.

Project leader: Dr Zoltán Giricz senior research associate