The molecular mechanisms underlying coronary arteries’ formation during development and cardiac neovascularization after injury are poorly understood. However, a detailed description of the functional transcription factors (TFs) regulating these processes and the signaling pathways remains incomplete. This study aims to identify the novel cardiac transcriptional mechanisms of vessel remodeling and coronary angiogenesis by defining the molecular signatures of coronary vascular endothelial cells.
The Nes-CreERT2 and Nes-gfp transgenic mouse lines were demonstrated to be novel tools for targeting sprouting coronary vessels and studying the emergence of coronary endothelium during development. Sox17 TF regulates Nestin’s enhancer’s transcriptional activation in developing coronary vessels while its genetic deletion leads to inadequate coronary artery formation. The lack of Sox17 cannot be compensated in coronary vessels by overexpression of the other SoxF factors as described in other tissues. Most of the analyzed hearts showed a lack of left coronary artery in the ventral surface, whereas the complete absence of right coronary artery in the dorsal part of the heart was uncommon.
In conclusion, the conditional deletion of coronECs during the initial sprouting phase revealed the crucial role of the Sox17 factor in the subsequent remodeling into mature arterioles and arteries, as well as correct colonization of developing plexus in embryonic hearts. The most robust phenotype showed a lack of developing coronary plexus in the ventral surface of mutant hearts.
Ref: https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.120.317121
