MEDICINE/ Caiado: how we discovered the protein that forms our blood vessels
Nearly 400 years ago, the English scientist William Harvey discovered the blood circulation but there are still many things to be understood about the cardiovascular system, one of the fundamental systems of the human body. For instance, the peculiar ability of blood vessels to form themselves again after a wound - that everybody has experimented at least some times had an unclear origin. At least up to some time ago, when Sergio Dias and Francisco Caiado and the research team at Instituto Gulbenkian de Ciência in Portugal have published the results of an intensive research programme on the online review Public Library of Science.
We have asked Francisco Caiado and Sergio Dias to explain details and applications of this research.
Which were the main hypotheses in order to explain the building mechanism of blood vessels?
There are two main ways for new blood vessel formation: angiogenesis and vasculogenesis. Angiogenesis is the processes by which new blood vessel are formed from activation and proliferation of pre-existing endothelial cells.
Vasculogenesis is the process by which new blood vessel form by differentiation of tissue resident progenitor cells into functional blood vessels. These two processes may occur simultaneously both in the adult and in developing embryos.
How did you arrive to your hypothesis about the role of the Notch protein ?
The role of the Notch pathway in blood vessel formation as been implicated in numerous studies, most of them showing that lack of the Notch proteins or their ligands (on endothelial cell) result in blood vessel abnormalities.
However the role of these proteins on progenitor cells during vasculogenesis was still undisclosed. Therefore it seems probable that these proteins might regulate progenitor cell function and consequently blood vessel formation.
How have you been able to prove the validity of your hypothesis?
The role of the Notch protein on progenitor cells during vasculogenesis was assessed using compounds that inhibit/activate the Notch pathway. Accordingly we activated and inhibited this pathway on the progenitor cells and assessed ther ability to participate in the vasculogenic process. Interestingly inhibitions of the pathway led to a decreased vasculogenic function while activation improved it.
Did you collaborate with other teams, universities or hospital institutes?
This work was done mainly in the Portuguese Institute of Oncology (IPO-CIPM), The Gulbenkian Institute for Science (IGC) and Molecular Medicine Institute (IMM).
Which are the most foreseeable applications? Are they more in the field of trauma consequences or of specific illnesses?
The applications are more directly related with skin wounding which can be trauma consequences or side effects of specific illnesses like diabetes.
Do you think it possible to find applications for congenital malformations?
No, I find it hard to associate any application in congenital malformations however a more profound knowledge of the Notch pathway might have such applications in the future.
Which application will need a shorter validation period and hence be ready for a real use by physicians?
The use of bone marrow derived progenitor cells to aid wound healing in diabetic and traumatic wounded patients might be most probable application.
Another possible application might be modulation of the Notch pathway on these cells prior to transplantation into wounded tissues.
The blood vessels structure is often mentioned as an example of application of fractals to the knowledge of the biological forms. In your opinion, is this just a suggestive image or is this a possible useful tool for the research and knowledge?
In your research did it have some influence , or might have in the future?
Blood vessels are difficult to study in the human body because the vasculature is a complex, highly branched, treelike structure embedded within three-dimensional opaque tissues. Therefore it is necessary to have different approaches to study this structure. Interestingly modern fractal mathematics is used to measure and model the morphological stimulation and inhibition of blood
vessel growth by molecular regulators of angiogenesis. So although it has no direct influence in my work it might help to comprehend blood vessel formation if coupled with the regular blood vessel imaging techniques.