Switch for VEGF-mediated angiogenesis identified
Munster – German and UK researchers have identified the Jagged1 protein as an on-switch for angiogenesis. A binary decision, determining the fate of a stem cell located on the inner wall of veins and arteries to differentiate into a bloodvessel cell, is made when the Jagged1 protein activates the transmembrane receptor protein Notch on neighbouring endothelial cells. In doing so, the ligand acts as a transducer in the Notch Signal Pathway (NSP), making cells succeptible to Vascular Endothelial Growth Factor (VEGF). VEGF then promotes the growth of new blood vessels. If Notch is not activated by Jagged1, VEGF does not have this effect on the stem cell. This is a mechanism which is used to control the process of bifurcation.
NSP regulates cell-cell communication, mediating cellular differentiation and tissue specific development in eukaryotes. Deregulation causes developmental defects in the networking and branching of blood vessels, which can lead to a disrupted flow of oxygen and nutrients to surrounding tissues. The scientists would like to induce vascularisation to counteract defects that can lead to different pathological indications, such as heart attack or cancer.
'For the first time, we now understand how these individual components work together,' commented Professor Ralf Adams of the Max Planck Institute for Molecular Biomedicine in Germany. 'In experiments on mice, we want to learn how to actively control the growth of blood vessels.' Ultimately, medicines could one day be used to do the same in people, he added.
Since NSP plays an important role in the development, growth and healing of many different types of tissues and organs though, the next step will be to investigate the possible dangers of manipulating Notch.