National Grants
Grant of the Romanian National Authority for Scientific Research and Innovation, CNCS – UEFISCDI, Program Human Resources/Project number PN-II-RU-TE-2014-4-0523: Grant no.80/01.10.2015/ 2015-2017 - Project leader Nicoleta Alexandru
Project Title: New insights in platelet-endothelial progenitor cell interplay in atherosclerotic disease
Acronim: NICAD
Project Director: Nicoleta Alexandru, PhD, Biochemist, Principal Investigator III (CSIII), Department: Pathophysiology and Pharmacology, Institute of Cellular Biology and Pathology ‘Nicolae Simionescu’, Bucharest, Romania
Team: Adriana Georgescu (PhD, biophysicist- CSI), Eugen Andrei (PhD-student,chemist-CS), Maria-Cristina Corotchi (PhD-student, biochemist-AC), Florentina Safciuc (PhD, biologist-CS), Emanuel Dragan (Vet doctor, CS), Marilena Isachi (technician)
Project summary
Endothelial progenitor cells (EPCs) and platelets have an important role in repair following vascular injury, and a link between them may deliver explanations for cellular mechanisms involved.Although are evidence suggesting that platelets are essential in EPC attracting, homing and differentiation, however, the platelet effects on EPC functions in atherosclerosis have received less attention.
Aim: The purpose of this project is to investigate the EPC-platelets relationship, and to follow the consequences of circulating EPC transplantation on this interaction in atherosclerosis. Experimental models: Golden Syrian hamsters will be divided in three groups: hypertensive-hypercholesterolemic (HH), HHtreated with EPCs (HH-EPCs) and control (C). Objectives: (1) the characterization of experimental hamster groups: HH, HH-EPCs, and C;(2) the quantification of circulating EPC levels and functions; (3) the evaluation of causal direct relationship between EPCs and platelets; (4) the molecular mechanisms investigation by which platelets influence circulating EPC functions.
Conclusion: The findings obtain in new experimental animal models will contribute to elucidating of the manner in which EPCs interact with platelet, critically to fully understand their potential therapeutic properties. Understanding and modulating the mechanisms that regulate both vascular regeneration and injury may lead to a promising therapeutic approach to treat patients at high risk for atherosclerotic disease.
Project Publications:
2015
Peer-review ISI articles:
1.Elisabeta Bădilă, Ana Maria Daraban, Emma Ţintea, Daniela Bartoş, Nicoleta Alexandru, Adriana Georgescu. Midkine in cardio-vascular disease: Where do we come from and where are we heading to?European Journal of Pharmacology, 762:464-471, 2015.
2.Josune Orbe, Nicoleta Alexandru, Carmen Roncal, Miriam Belzunce, Paula Bibiot, Jose A Rodriguez, Joost C Meijers, Adriana Georgescu, Jose A Paramo. Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke. Thrombosis Research, 136: 445–450, 2015.
3.Nicoleta Alexandru, Ana Costa, Alina Constantin, Daniel Cochior, Adriana Georgescu. Microparticles: from biogenesis to biomarkers and diagnostic tools in cardiovascular disease. – in revision – Current Stem Cell Research and Therapy.
Peer-review articles indexed in international database:
1. Nicoleta Alexandru, Adriana Georgescu. Microparticles as players in the pathogenesis of cardiovascular disease. Fisiología, 2015, vol. 18(1):9-14. ISSN:1889-397X.
2. Eugen Andrei, Nicoleta Alexandru, Adriana Georgescu.Circulating microparticles: major mediators of the pathogenesis of cardiovascular complications in diabetes. Annals of the Romanian Society for Cell Biology, Volume XIX, Issue 3, pp. 55-63, 2015.
Awards
National Prizes:
1. Award offered by Ministry of Education and Scientific Research – November 2015 for the paper ‘Interaction of platelets with endothelial progenitor cells in the experimental atherosclerosis: Role of transplanted endothelial progenitor cells and platelet microparticles’ in Biology of the Cell, Vol. 107(6): 189–204, 2015. (Nicoleta Alexandru, Eugen Andrei, Emanuel Dragan, and Adriana Georgescu).
2. Award offered by Ministry of Education and Scientific Research Ministry for Education and Research – November 2015 for the paper ‘Midkine in cardio-vascular disease: Where do we come from and where are we heading to?’ in European Journal of Pharmacology, 762:464-471, 2015. (Elisabeta Bãdilã, Ana Maria Daraban, Emma Ţintea, Daniela Bartoş,Nicoleta Alexandru, Adriana Georgescu).
2016
Articles published in ISI Journals:
1. Nicoleta Alexandru,Elisabeta Badila, Emma Weiss, Daniel Cochior, Ewa Stępień, Adriana Georgescu. Vascular complications in diabetes: microparticles and microparticle associated microRNAs as active players. Biochemical and Biophysical Research Communications, 472: 1-10, 2016.
2. Adriana Georgescu*, Nicoleta Alexandru*, Eugen Andrei, Emanuel Dragan, Daniel Cochior, Sergio Dias. Effects of transplanted circulating endothelial progenitor cells and platelet microparticles in atherosclerosis development. Biology of the Cell, 108(8):219-243, 2016. (*These authors contributed equally to this work).
3. Miruna Nemecz*, Nicoleta Alexandru*, Gabriela Tanko, Adriana Georgescu. Role of microRNA in endothelial dysfunction and hypertension, Current Hypertension Reports, 18(12):87, 2016. (*These authors contributed equally to this work).
Science newspaper article
Nicoleta Alexandru, Adriana Georgescu. Active role of cell-derived microparticles in diabetes associated cardiovascular complications. Atlas of Science (website: www.atlasofscience.org), August 12, 2016.
Abstracts published in ISI Journals:
1. Nicoleta Alexandru, Emanuel Dragan, Eugen Andrei, Loredan Niculescu, Adriana Georgescu. Microparticles of healthy origins improve atherosclerosis-associated endothelial progenitor cell dysfunction via microRNA transfer. Poster presentation at the Frontiers in Cardiovascular Biology 2016 meeting, Florence, Italy, 08–10 July, 2016, Abstract No. 153, in the Cardiovascular Research, Volume 111, Issue suppl 1, Pp. S30, 2016.
2. Adriana Georgescu, Nicoleta Alexandru, Eugen Andrei, Emanuel Dragan, Florentina Safciuc, Ana Maria Daraban, Elisabeta Badila. Circulating microparticles of healthy origins protect against atherosclerotic vascular disease via microRNA transfer to endothelial progenitor cells. Presentation at the Frontiers in Cardiovascular Biology 2016 meeting, Florence, Italy, 08–10 July, 2016, Abstract No. 257 in the Cardiovascular Research, Volume 111, Issue suppl 1, Pp. S49, 2016.
Communications (Posters) presented at international scientific meetings:
1. Nicoleta Alexandru, Emanuel Dragan, Eugen Andrei, Violeta Ristoiu, Loredan Niculescu, Adriana Georgescu. Microparticles as microRNAs messengers improving atherosclerosis-associated endothelial progenitor cells dysfunction. The 8th National Congress with international participation and 34th Annual scientific session of the Romanian Society for Cell Biology, June 08-12, 2016, Oradea (RO), Abstract in Bulletin of RSCB No. 44, p. 77.
2. Nicoleta Alexandru, Eugen Andrei, Emanuel Dragan, Florentina Safciuc, Ana Maria Daraban, Elisabeta Badila, Adriana Georgescu. Microparticles as intracellular delivery strategies for microRNAs and potential therapies for atherosclerotic vascular disease. The 8th National Congress with international participation and 34th Annual scientific session of the Romanian Society for Cell Biology, June 08-12, 2016, Oradea (RO), Abstract in Bulletin of RSCB No. 44, p.78.
3. Nicoleta Alexandru, Emanuel Dragan, Eugen Andrei, Loredan Niculescu, Adriana Georgescu. Microparticles of healthy origins improve atherosclerosis-associated endothelial progenitor cell dysfunction via microRNA transfer. The Frontiers in Cardiovascular Biology 2016 meeting, Florence, Italy, 08–10 July, 2016, Abstract No. 153, in the Cardiovascular Research, Volume 111, Issue suppl 1, Pp. S30, 2016.
4. Nicoleta Alexandru, Eugen Andrei, Emanuel Dragan, Violeta Ristoiu, Adriana Georgescu. The effects of circulating endothelial progenitor cell and platelet microparticle administration on platelet-endothelial progenitor cell interplay in atherosclerotic disease. The 15th Biennial Meeting of the International Society for Applied Cardiovascular Biology’ (ISACB), Banff, Alberta, Canada, 7-10 September 2016, Abstract No. P21, p.18.
5. Adriana Georgescu, Nicoleta Alexandru,Eugen Andrei, Emanuel Dragan, Sergio Dias. Circulating endothelial progenitor cells of healthy origins and platelet microparticles of hypertensive-hypercholesterolemic origins play opposite roles in atherosclerosis development. The 15th Biennial Meeting of the International Society for Applied Cardiovascular Biology’ (ISACB), Banff, Alberta, Canada, 7-10 September 2016, Abstract No. P22, p.19.
Awards
National Prizes:
Award offered by Ministry of Education and Research Ministry– December 2016 for the paper: ‘Effects of transplanted circulating endothelial progenitor cells and platelet microparticles in atherosclerosis development’ in Biology of the Cell, Vol. 108(8):219-243, 2016. (Adriana Georgescu, Nicoleta Alexandru, Eugen Andrei, Emanuel Dragan, Daniel Cochior, Sergio Dias)
2017
Articles published in ISI Journals:
1. N. Alexandru, A. Costa, A. Constantin, D. Cochior, A. Georgescu. Microparticles: From biogenesis to biomarkers and diagnostic tools in cardiovascular disease. Current Stem Cell Research & Therapy. 12(2):89-102, 2017.
2. N. Alexandru, E. Andrei, L. Niculescu, E. Dragan, V. Ristoiu, A. Georgescu. Microparticles of healthy origins improve endothelial progenitor cell dysfunction via microRNA transfer in an atherosclerotic hamster model, Acta Physiologica, 221: 230–249, 2017.
Journals indexed in international databases:
A. Costa, N. Alexandru, F. Silva, A. Magalhães, S. Dias, A. Georgescu. Detection of miRNAs in Extracellular Vesicles by In Situ Hybridization Using Formalin-Frozen Paraffin Embedded Sections. Annals of Romanian Society for Cell Biology, Vol. XXI, Issue 3, pp. 29-35, 2017.
Chapters in books:
N. Alexandru, I. Titorencu, S. Frunzã, E. Weiss, E. Bãdilã, A. Georgescu. Chapter's Title: Endothelial progenitor cell dysfunction in the pathogenesis of vascular complications of diabetes. Book's Title: Mechanisms of Vascular Defects in Diabetes Mellitus, Editors: ChandrasekharanKartha, Surya Ramachandran, M. Radhakrishna Pillai, in Series Title: Advances in Biochemistry in Health and Disease, Springer, UK, Volume 17, ISBN 978-3-319-60323-0, p.159-208, 2017.
Abstracts published in ISI Journals:
1. N. Alexandru, E. Dragan, V. Ristoiu, L. Niculescu, A. Georgescu. Role of microparticles as microRNA messengers in reestablishing of atherosclerosis-associated endothelial progenitor cell dysfunction. Presentation as Science at a Glance at the ‘85th European Atherosclerosis Society Congress’ (EAS2017), Prague, Czech Republic, 23-26 April 2017, Abstract SAG014, in Atherosclerosis, August issue, Volume 263, Page e33 (2017). DOI:http://dx.doi.org/10.1016/j.atherosclerosis.2017.06.127.
2. A. Georgescu, N. Alexandru, E. Dragan, F. Safciuc, A.M. Daraban, E. Badila. Endothelial progenitor cells - derived microparticles reproduce the favorable role of their parent cells of healthy origins in the treatment of atherosclerosis via microRNA transfer. Presentation as Science at a Glance at the ‘85th European Atherosclerosis Society Congress’ (EAS2017), Prague, Czech Republic, 23-26 April 2017, Abstract SAG050 in Atherosclerosis, August issue, Volume 263, Page e48 (2017). DOI: http://dx.doi.org/10.1016/j.atherosclerosis.2017.06.163.
3.N. Alexandru, E. Andrei, E. Dragan, M. Nemecz, A. Constantin, A. Georgescu, M. Simionescu. Platelets stimulate the functional properties of late endothelial progenitor cells in atherosclerosis. Poster presentation at the ‘42ND The Federation of European Biochemical Societies’ (FEBS 2017)meeting, Ierusalim, Israel, 10-14 September, 2017. Abstract No. P.1.5-037 in The FEBS Journal 284 (Suppl. 1), 104–392, Page 132 (2017). DOI: 10.1111/febs.14174
4.A. Georgescu, N. Alexandru, E. Andrei, E. Dragan, F. Safciuc, S. Frunza, M. Dumitrescu, G. Tanko, E. Badila. Normal cell derived microparticles used as delivery system for microRNAs protect against atherosclerotic vascular disease. Poster presentation at the ‘42ND The Federation of European Biochemical Societies (FEBS 2017) meeting, Ierusalim, Israel, 10-14 September, 2017. Abstract No. P.1.5-036 in The FEBS Journal 284 (Suppl. 1), (2017), 104–392, page 132. DOI: 10.1111/febs.14174.
5. M. Nemecz, A. Constantin,M. Dumitrescu, N. Alexandru, A. Picu, B. Smeu, G. Tanko, M. Simionescu.Beta cells exposed to sera from obese diabetic patients undergoing improved glycaemic control exhibit enhanced survival and diminished formation of reactive oxygen species. Poster presentation at the 53rd Annual Meeting of European Association for the Study of Diabetes (EASD), 2017, Lisbon, 11-15 September. Abstract No. 442 in Diabetologia, 60 (Suppl 1):S1–S608, page S202, (2017).
Communications (Posters) presented at international scientific meetings:
N. Alexandru, E. Dragan, Miruna Nemecz, Madalina Dumitrescu, Adriana Georgescu. Interaction with platelets of healthy origins augments the functional properties of late endothelial progenitor cells in experimental induced atherosclerosis. Poster at the 9th National Congress with international participation and 35th Annual scientific session of the Romanian Society for Cell Biology, June 7-10 iunie, 2017, Iasi (RO), Abstract in Bulletin of RSCB No. 45, Poster 66, p. 104.
Awards
National Prizes:
1. ‘Scientific Achievements – Original Article’ Award offered by Executive Agency for Higher Education, Research, Development and Innovation Funding - UEFISCDI and Ministry for Education and Ministry of Research and Innovation– October 2017 for the paper ‘Role of microRNA in endothelial dysfunction and hypertension’ in Current Hypertension Reports, 18(12):87, 2016. (M. Nemecz*, N. Alexandru*, G. Tanko, A. Georgescu).
2. ‘Scientific Achievements – Original Article’ Award offered by Ministry for Education and Research – June 2018 for the paper ‘Microparticles of healthy origins improve endothelial progenitor cell dysfunction via microRNA transfer in an atherosclerotic hamster model’ in Acta Physiologica, 221, 230-249, 2017. (N. Alexandru, E. Andrei, L. Niculescu, E. Dragan, V. Ristoiu, A. Georgescu).
