Interplay between BMP2 and Notch signaling in endothelial-mesenchymal transition: implications for cardiac fibrosis

Pavel Docshin; Ahmad Bairqdar; Anna Malashicheva

doi:10.21037/sci-2023-019

Interplay between BMP2 and Notch signaling in endothelial-mesenchymal transition: implications for cardiac fibrosis

Stem Cell Investig. 2023 Sep 28:10:18. doi: 10.21037/sci-2023-019. eCollection 2023.

Authors

Pavel Docshin^{1

2}, Ahmad Bairqdar², Anna Malashicheva²

Affiliations

¹ Laboratory of Molecular Cardiology, Institute of Molecular Biology and Genetics, Almazov National Medical Research Centre, Saint Petersburg, Russia.
² Laboratory of Regenerative Biomedicine, Institute of Cytology, Russian Academy of Science, Saint Petersburg, Russia.

Abstract

Background: The endothelial-to-mesenchymal transition (EndoMT) is a crucial process in cardiovascular development and disorders. Cardiac fibrosis, characterized by excessive collagen deposition, occurs in heart failure, leading to the organ remodeling. Embryonic signaling pathways such as bone morphogenetic protein 2 (BMP2) and Notch are involved in its regulation. However, the interplay between these pathways in EndoMT remains unclear.

Methods: This study investigates the downstream targets of Notch and BMP2 and their effect on EndoMT markers in cardiac mesenchymal cells (CMCs) and human umbilical vein endothelial cells (HUVECs). We transduced cell cultures with vectors carrying intracellular domain of NOTCH1 (NICD) and/or BMP2 and evaluated gene expression and activation of EndoMT markers.

Results: The results suggest that the Notch and BMP2 signaling pathways have common downstream targets that regulate EndoMT. The activation of BMP2 and Notch is highly dependent on cell type, and co-cultivation of CMCs and HUVECs produced opposing cellular responses to target gene expression and α-smooth muscle actin (α-SMA) synthesis.

Conclusions: The balance between Notch and BMP2 signaling determines the outcome of EndoMT and fibrosis in the heart. The study's findings highlight the need for further research to understand the interaction between Notch and BMP2 in the heart and develop new therapeutic strategies for treating cardiac fibrosis.

Keywords: BMP2 signaling pathway; Endothelial-to-mesenchymal transition (EndoMT); Notch signaling; cardiac fibrosis; cardiac mesenchymal cells (CMCs).