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Grant of the Romanian National Authority for Scientific Research and Innovation, CNCS – UEFISCDI, Program Human Resources/Project number PN-II-RU-TE-2014-4-0525: Grant no.79/01.10.2015/ 2015-2017 - Project leader Adriana Georgescu

Project Title:Microparticles as intracellular delivery strategies for microRNAs and potential therapies for atherosclerotic vascular disease

Acronim: MISTAD

Project Director: Adriana Georgescu, PhD-Habil Degree, Biophysicist, Principal Investigator I (CSI), Group Leader, Department: Pathophysiology and Pharmacology, Institute of Cellular Biology and Pathology ‘Nicolae Simionescu’, Bucharest, Romania

Team: Nicoleta Alexandru (PhD, biochemist-CSIII), 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

The development of atherosclerosis and cardiovascular disease is the result of multiple intermediate processes where endothelial dysfunction and vascular inflammation play key contributing roles. Cell-derived microparticles (MPs), endothelial progenitor cells (EPCs) and circulating microRNAs (miRNAs) have attracted major interest as biomarkers and potential regulatorsfor atherosclerotic vascular disease, but their involvement in the mechanisms of inflammatory processes and vascular repair remain controversially.

The project goal will be to demonstrate that in atherosclerotic vascular disease: (1) MPs operate as protective and delivery system for miRNAs in circulation; (2) miRNA profile in MPs is different from their maternal cells and is disease-specific; (3) MPs transfer genetic information from MP-releasing cells to EPCs mediating their function. We will also bring evidence concerning the differences in miRNA transfer by MPs and EPC-derived MPs.

Our data will indicate that MPs, particularly EPC-derived MPs, are capable of transferring a subset of miRNAs into circulation targeting EPCs and vascular endothelium, suggesting a tightly regulated transfer process. Besides, we may promote the idea that MPs and EPC-derived MPs are able to program stem/progenitor cells to repair vascular injuries by miRNA content, suggesting that they could be exploited as a potential new therapeutic approach in atherosclerotic vascular disease giving hope to patients with cardiovascular disease.

 

Project Publications

2015

Peer-review ISI articles:

1.Nicoleta Alexandru, Eugen Andrei, Emanuel Dragan, Adriana Georgescu.  Interaction of platelets with endothelial progenitor cells in the experimental atherosclerosis; the role of transplanted endothelial progenitor cells and platelet microparticles. Biology of The Cell, 107(6): 189–204, 2015.

2.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.

3.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.

4.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.

 

Oral Communications at international scientific meetings

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. 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)