Reference : Network-based Approach Enabling Drug Repositioning for the Treatment of Myocardial In...
Dissertations and theses : Bachelor/master dissertation
Life sciences : Multidisciplinary, general & others
Network-based Approach Enabling Drug Repositioning for the Treatment of Myocardial Infarction
Androsova, Ganna mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
University of Luxembourg, ​Luxembourg, ​​Luxembourg
Master in Integrated Systems Biology (Académique)
Azuaje, Francisco mailto
Schneider, Reinhard mailto
Nazarov, Petr mailto
Krause, Roland mailto
[en] myocardial infarction ; cryoinjury ; zebrafish model ; WGCNA ; heart regeneration
[en] Despite a notable reduction in incidence of acute myocardial infarction (MI), patients who experience it remain at risk for premature death and cardiac malfunction. The human cardiomyocytes are not able to achieve extensive regeneration upon MI. Remarkably, the adult zebrafish is able to achieve complete heart regeneration following amputation, cryoinjury or genetic ablation. This raises new potential opportunities on how to boost the heart healing capacity in humans. The objective of our research is to characterize the transcriptional network of the zebrafish heart regeneration, to describe underlying regulatory mechanisms, and to identify potential drugs capable to boost heart regeneration capacity.
Having identified the gene co-expression patterns in the data from a zebrafish cryoinjury model, we constructed a weighted gene co-expression network. To detect candidate functional sub-networks (modules), we used two different network clustering approaches: a density-based (ClusterONE) and a topological overlap-based (Dynamic Hybrid) algorithms.
We identified eighteen distinct modules associated with heart recovery upon cryoinjury. Functional enrichment analysis displayed that the modules are involved in different cellular processes crucial for heart regeneration, including: cell fate specification (p-value < 0.006) and migration (p-value < 0.047), cardiac cell differentiation (p-value < 3E-04), and various signaling events (p-value < 0.037). The visualization of the modules’ expression profiles confirmed the relevance of these functional enrichments. Among the candidate hub genes detected in the network, there are genes relevant to atherosclerosis treatment and inflammation during cardiac arrest. Among the top candidate drugs, there were drugs already reported to play therapeutic roles in heart disease, though the majority of the drugs have not been considered yet for myocardial infarction treatment.
In conclusion, our findings provide insights into the complex regulatory mechanisms involved during heart regeneration in the zebrafish. These data will be useful for modeling specific network-based responses to heart injury, and for finding sensitive network points that may trigger or boost heart regeneration in the zebrafish, and possibly in mammals.
Centre de Recherche Public de la Santé - CRP SANTE
Fonds National de la Recherche - FnR
Researchers ; Students ; General public

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