Shruti Sharma
Postgraduate Institute of Medical Education and Research, IndiaPresentation Title:
A plausible role of exosomal miR-24-2 in mitral valve dysfunction during rheumatic heart disease pathogenesis (RHD)
Abstract
Background: RHD is an autoimmune disease that results in permanent mitral valves damage. The endothelial cells in valves, undergo Endo MT, forming, myo-fibroblasts. These mesenchymal cells elevates TGF-β levels in HUVECs and results in fibrosis and valves dysfunction. The role of exosomal miRNAs, in Endo MT and valves fibrosis, during RHD is unknown.
Aim: To unfurl the role of exosomal miRNA in mitral valves damage during RHD.
Objectives:
1. To isolate and characterize exosomes from:
a. Serum and Pericardial fluid (PF) of RHD patients
b. Media of RHD patient serum stimulated- HUVECs
2. To study the role of exosomes during EndoMT in HUVECs
3. To profile miRNAs from isolated exosomes and validate their expressions in the samples
4.To investigate the functional role of these miRNAs in HUVECs
Materials & Methods: Exosomes were isolated and characterised from serum and PF of RHD patients and media. EndoMT markers expressions were checked in RHD patient exosomes (R-exo) treated HUVECs in comparison to normal individual exosomes (N-exo) treated HUVECs to check whether exosomes play any role in EndoMT and fibrosis. MicroRNA profiling of exosomal RNA revealed that miR-24-2 RNA levels were attenuated in patient samples. Functional inhibition study was performed, to check for EndoMT and fibrosis markers, via RT-PCR and it was confirmed by RNA expression levels and protein levels western blotting) in the mitral valves of RHD patients.
Results: Decreased levels of miR-24-2 as well as endothelial markers and increased levels of mesenchymal and fibrosis markers was observed in R-exo-treated HUVECs, and, was associated with the altered proteins levels in mitral valves of patients.
Conclusion: These findings suggest a role of exosomal miR-24-2 in Endo MT and mitral valves fibrosis, during RHD.
Biography
Dr. Shruti did her Bsc/Msc.in Biotechnology from Panjab University, Chandigarh, India and completed her PhD, from Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh in 2021. She has been working as senior demonstrator, in the department of Biophysics, from the same institute. She has published research articles in Medline/Scopus/Wos indexed journals.
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