Project's code: PN-III-P4-ID-PCE-2020-1340
Project's title: Fundamental mechanisms of post-infarction remodeling in old heart at fibroblast population level
Contract number: PCE122/12.02.2021
Coordinator: Alexandrina Burlacu
Team members: Evelyn Gabriela Rusu, Catalina Marinescu, Mihai Bogdan Preda
Budget: 1.197.912 Lei
Period: 04.01.2021 – 31.12.2023
Cardiovascular diseases (CVD) are the major cause of mortality in the world, with myocardial infarction (MI)-based injury and subsequent heart failure as major sequels of this disorder. Despite the importance of fibrosis in CVD, the contribution of cardiac fibroblasts (cFb) to disease progression remains poorly understood and interventions effectively targeting this cell have only recently emerged in the spotlight. In-fOLD project focuses on the active role of cFb in the ventricular remodeling of old animals and aims to unveil cFb-specific signaling pathways in natural ageing process upon interference with MI and cell therapy. The objectives of the project are: (i) Generate reference transcriptome of cFb derived from old mice with MI; (ii) Identify changes in cFb-specific signaling cascades induced by cell therapy post-MI; (iii) Provide insights into the role of cFb in modulation of the reparatory process of MI in old mice. The first two objectives are expected to provide data about the molecular changes over the MI time course that produce the impaired responsiveness of cFb in old individuals. By the third objective, the cardiac repair in old animals will be addressed as a T cell-mediated phenomenon, by focusing on the crosstalk between cFb and T cells in vitro, which has not been carried out before. These studies will provide a more integrated view of cardiac biology by illustrating the role of different cell types in the cardiac repair process after MI in old organisms.
Dissemination of results
Rusu-Nastase EG, Lupan AM, Marinescu CI, Neculachi CA, Preda MB, Burlacu A. MiR-29a Increase in Aging May Function as a Compensatory Mechanism Against Cardiac Fibrosis Through SERPINH1 Downregulation. Front Cardiovasc Med. 2022; 8:810241. doi: 10.3389/fcvm.2021.810241. PMID: 35118144
Lupan AM*, Rusu EG*, Preda MB, Marinescu CI, Ivan C, Burlacu A. miRNAs generated from Meg3-Mirg locus are downregulated during aging. Aging (Albany NY). 2021;13(12):15875-15897. doi: 10.18632/aging.203208. PMID: 34156971.
Marinescu CI, Preda MB, Burlacu A. A procedure for in vitro evaluation of the immunosuppressive effect of mouse mesenchymal stem cells on activated T cell proliferation. Stem Cell Res Ther. 2021;12(1):319. doi: 10.1186/s13287-021-02344-3. PMID: 34090507.
Marinescu CI, Preda MB, Neculachi CA, Rusu EG, Popescu S, Burlacu A. Identification of a hematopoietic cell population emerging from mouse bone marrow with proliferative potential in vitro and immunomodulatory capacity. Front Immunol. 2021;12:698070. doi: 10.3389/fimmu.2021.698070. PMID: 34413852.
Presentations at international scientific conferences:
Burlacu A. Exploring new pathways in age-related heart diseases. Oral presentation, ERA-Net on Cardiovascular Diseases (ERA-CVD), Riga, Letonia, 18-21 September, 2022.
Nastase-Rusu EG., Lupan AM., Preda MB., Marinescu CI, Neculachi CA., Burlacu A. Natural aging process is associated with increased mir-29a and downregulated serpinh1 in multiple organs. Oral presentation. the 38th Annual Session of the Romanian Society of Cellular Biology, 21-23 Octomber 2022, Cluj-Napoca.
Marinescu C, Preda MB, Burlacu A. A procedure for the in vitro evaluation of the immunosuppressive effect of mesenchymal stem cells. Poster presented at ,,2nd Olympiad in Cardiovascular Medicine - International Symposium on Experimental and Clinical Cardiology”, Heraklion, Grecia, 25 April -1 Mai 2022.
Rusu EG, Lupan AM, Preda MB, Marinescu CI, Burlacu A. MiRNAs generated from Meg3-Mirg locus are downregulated during aging. Poster presented at ,,2nd Olympiad in Cardiovascular Medicine - International Symposium on Experimental and Clinical Cardiology”, Heraklion, Grecia, 25 April-1 Mai 2022.
Burlacu A. Stem cell therapy for myocardial regeneration. Oral presentation, IRCCS Ospedale San Raffaele, Millano, August 30, 2021.
Rusu EG, Lupan AM, Preda MB, Marinescu CI, Burlacu A. MiRNAs generated from Meg3-Mirg locus are downregulated during aging. Oral presentation, the 38th Annual Session of the Romanian Society of Cellular Biology, November 4-6, 2021, Online Congress.
Burlacu A., Marinescu CI, Preda MB. Two distinct cell populations initiated from mouse bone marrow in culture with proliferative potential and immunomodulatory capacity, poster presented at the Virtual Conference „Innovative Tissue Therapies from Bench to Bedside”, organized by Nature Communications, November 16-18, 2021.