How is the heart formed in mammals? What role do endothelial cells play? Do the same pathways and genes that participate in the formation of the embryonic heart also participate in the repair processes?
A new study by a team from the Faculty of Biology and the Institute of Biomedicine (IB) of the University of Barcelona (UB) reveals that deletion of the Wt1 gene in endothelial cells during the early phases of coronary vessel formation affects to the correct development of the heart.
The research was directed by Professor Ofelia Martínez-Estrada, from the Department of Cellular Biology, Immunology and Physiology of the Faculty of Biology, and a member of the IB and the Celltec UB research group. In the study, whose first author is the researcher Marina Ramiro-Pareta (IB, UB), teams from the Faculty of Medicine and Health Sciences and the Institute of Neurosciences of the UB (UBneuro), the Institute of Research Germans Trias i Pujol (IGTP), the Autonomous University of Barcelona (UAB), the National Center for Genomic Analysis (CNAG) and the Biomedical Network Research Center for Cardiovascular Diseases (CIBERCV), in Spain.
New perspectives on the functions of the Wt1 gene
Endothelial cells form the inner cell layer of blood vessels and have a wide range of essential functions in the development of tissues and organs such as the highly vascularized heart. In the cardiovascular system, the Wt1 gene shows a high level of expression in the epicardium —the outer layer of the heart— and in the endothelial cells of this organ.
“Until now, it was thought that the defects in the formation of the embryonic heart observed in the Wt1KO transgenic mouse models – that is, lacking this gene – were mainly due to the functions of this gene in the epicardium”, explains Professor Ofelia Martinez-Estrada. “Now,” adds Martínez-Estrada, “our work shows that the deletion of the Wt1 gene in the endothelial cell affects the formation of coronary vessels and the development of the myocardium.”
In the study, carried out with animal models, the researchers have combined image analysis and RNA-Seq techniques, which have made it possible to identify how the deletion of Wt1 in coronary endothelial cells during the early stages of development modifies the transcriptional signature — that is, the different genetic expressions—of these cell types.
“In particular, many of the genes that are modified in these Wt1KO cells are genes that are dynamically modulated throughout coronary endothelial cell development. These transcriptional changes are correlated with defects in the formation and differentiation of arteries and veins, as well as with a decrease in the proliferation of cardiomyocytes, two processes that are determinant for the correct development of the embryonic heart”, explains the researcher Marina Ramiro-Pareta. .
From left to right, the researchers Ofelia Martínez Estrada and Marina Ramiro Pareta, from the Department of Cell Biology, Immunology and Physiology of the Faculty of Biology of the UB and the IB. (Photo: UB)
Revascularize the heart after a heart attack
The formation of new blood vessels after a myocardial infarction is essential for the survival of damaged tissue. Although various therapeutic strategies aimed at stimulating myocardial angiogenesis after a heart attack have been adopted in recent years, there are still no effective therapies to modulate the de novo vascularization process, which in the case of mammals is insufficient.
“The results of the new work have a number of relevant implications within the field of study of heart development. In addition, they also confirm the need to promote more research on the role of the Wt1 gene in endothelial cells in the revascularization processes of ischemic hearts”, concludes Professor Ofelia Martínez-Estrada.
The study is titled “Endothelial deletion of Wt1 disrupts coronary angiogenesis and myocardium development.” And it has been published in the academic journal Development, being highlighted by the editorial team in the “Research Highlight” section of that journal. (Source: UB)