Circulating ectosomes: Determination of angiogenic microRNAs in type 2 diabetes

Ewa Ł. Stępień^1✉, Martyna Durak-Kozica¹, Agnieszka Kamińska¹, Marta Targosz-Korecka², Marcin Libera³, Grzegorz Tylko⁴, Agnieszka Opalińska⁵, Maria Kapusta⁶, Bogdan Solnica⁶, Adriana Georgescu⁷, Marina C. Costa⁸, Agnieszka Czyżewska-Buczyńska⁹, Wojciech Witkiewicz⁹, Maciej T. Małecki¹⁰, Francisco J. Enguita^8✉

1. Department of Medical Physics, M. Smoluchowski Institute of Physics, Jagiellonian University, Kraków, Poland
2. Department of Physics of Nanostructures and Nanotechnology, Institute of Physics Jagiellonian University, Kraków, Poland
3. Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Zabrze, Poland
4. Department of Cell Biology and Imaging Institute of Zoology, Jagiellonian University
5. Institute of High Pressure Physics, Polish Academy of Science, Warsaw, Poland
6. Department of Clinical Biochemistry, Jagiellonian University Medical College, Kraków, Poland
7. Department of Pathophysiology and Pharmacology, Institute of Cellular Biology and Pathology, 'Nicolae Simionescu' of Romanian Academy, Bucharest, Romania
8. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal
9. WroVasc - Integrated Cardiovascular Centre, Regional Specialist Hospital, Research and Development Centre, Wroclaw, Poland
10. Department of Metabolic Disease, Jagiellonian University Medical College, Kraków, Poland

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Citation:
Stępień EŁ, Durak-Kozica M, Kamińska A, Targosz-Korecka M, Libera M, Tylko G, Opalińska A, Kapusta M, Solnica B, Georgescu A, Costa MC, Czyżewska-Buczyńska A, Witkiewicz W, Małecki MT, Enguita FJ. Circulating ectosomes: Determination of angiogenic microRNAs in type 2 diabetes. Theranostics 2018; 8(14):3874-3890. doi:10.7150/thno.23334. Available from http://www.thno.org/v08p3874.htm

Abstract

Ectosomes (Ects) are a subpopulation of extracellular vesicles formed by the process of plasma membrane shedding. In the present study, we profiled ectosome-specific microRNAs (miRNAs) in patients with type 2 diabetes mellitus (T2DM) and analyzed their pro- and anti-angiogenic potential.

Methods: We used different approaches for detecting and enumerating Ects, including atomic force microscopy, cryogenic transmission electron microscopy, and nanoparticle tracking analysis. Furthermore, we used bioinformatics tools to analyze functional data obtained from specific miRNA enrichment signatures during angiogenesis and vasculature development.

Results: Levels of miR-193b-3p, miR-199a-3p, miR-20a-3p, miR-26b-5p, miR-30b-5p, miR-30c-5p, miR-374a-5p, miR-409-3p, and miR-95-3p were significantly different between Ects obtained from patients with T2DM and those obtained from healthy controls.

Conclusion: Our results showed differences in the abundance of pro- and anti-angiogenic miRNAs in Ects of patients with T2DM, and are suggestive of mechanisms underlying the development of vascular complications due to impaired angiogenesis in such patients.

Keywords: angiogenesis, diabetes, extracellular vesicles, microRNA, systems biology