How is the mammals’ heart formed? What role do endothelial cells play? Do the identical pathways and genes involved within the formation of the embryonic heart also play a task in repair processes? A recent study conducted by a team from the Faculty of Biology and the Institute of Biomedicine of the UB (IBUB) reveals that the deletion of the Wt1 gene in endothelial cells through the early stages of coronary vessel formation affects the proper development of the guts in embryonic stages.
The study, featured within the Research Highlight section of the journal Development, is led by Professor Ofelia Martínez-Estrada, from the Department of Cell Biology, Immunology and Physiology of the Faculty of Biology, member of the IBUB and the Celltec UB research group. The article, whose first writer is the researcher Marina Ramiro-Pareta (UB-IBUB), also involves teams from the Faculty of Medicine and Health Sciences and the UB Institute of Neurosciences (UBNeuro), the Germans Trias i Pujol Research Institute (IGTP), the Autonomous University of Barcelona (UAB), the National Centre for Genomic Evaluation (CNAG-CRG) and the Centre for Biomedical Research Network on Cardiovascular Diseases (CIBERCV).
Recent perspectives on Wt1 gene functions
Endothelial cells form the inner cell layer of blood vessels and have a wide selection of essential functions in the event of tissues and organs corresponding to the guts, a highly vascularized organ. Within the cardiovascular system, the Wt1 gene is very expressed within the epicardium -;the outer layer of the heart-; and within the endothelial cells of this organ.
To this point, it was thought that the defects in embryonic heart formation observed in Wt1KO transgenic mouse models –i.e. mice lacking this gene – were mainly on account of the functions of this gene within the epicardium. Now, our study shows that deletion of the Wt1 gene within the endothelial cell affects coronary vessel formation and myocardial development”.
Professor Ofelia Martínez-Estrada
On this study, carried out on animal models, the researchers combined image evaluation and RNA-Seq techniques to discover how the deletion of Wt1 in coronary endothelial cells through the early stages of development modifies the transcriptional signature -;i.e. the several gene expressions-; of those cell types.
“Specifically, most of the genes found to be modified in these Wt1KO cells are genes which might be dynamically modulated throughout the event of coronary endothelial cells. These transcriptional changes correlate with defects within the formation and differentiation of arteries and veins, in addition to with a decrease in cardiomyocyte proliferation, two processes which might be crucial for the proper development of the embryonic heart”, states researcher Marina Ramiro-Pareta.
Revascularizing the guts after a heart attack
The formation of latest blood vessels after a myocardial infarction is important for the survival of the damaged tissue. Although various therapeutic strategies aimed toward stimulating myocardial angiogenesis after a cardiac infarction have been adopted in recent times, there are still no effective therapies to modulate the means of de novo vascularization, which is insufficient in mammals.
“The outcomes of the brand new study have a lot of necessary implications for the sector of cardiac development. Additionally they confirm the necessity for further research into the role of the Wt1 gene in endothelial cells within the revascularization processes of ischaemic hearts”, concludes Professor Ofelia Martínez-Estrada.
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Journal reference:
Ramiro-Pareta, M., et al. (2023). Endothelial deletion of Wt1 disrupts coronary angiogenesis and myocardium development. Development. doi.org/10.1242/dev.201147.