“These cells might play an important role in CVD”

martin_ramirezJavier Martin-Ramirez has done his PhD study at the University of Leiden. During his studies he has focused on the role of FcγRIIB in autoimmunity. J. Martin-Ramirez works as a Post Doc at the Department of Plasma Proteins (PP).

Can you tell us something about your current research here at Sanquin?
One of the projects I am working on is about non-coding RNAs, more particularly to check this type of profiles in different patients and their healthy first-degree relatives via microarrays. We have especially focused on Blood Outgrowth Endothelial Cells (BOECs) from peripheral blood. We have isolated the cells for further sample screening. The aim of this project is to search for differences in the microarray profile and try to use them as biomarkers. We hypothesize that patients present a distinctive pattern comparing to healthy controls. This research is important to predict, for example, subclinical-CVD (cardiovascular diseases) individuals that might have a heart attack caused by the atherosclerotic plaque formation. In this process a lot of cells are involved, including those endothelial cells that are in the peripheral blood. BOECs have a very powerful vasculogenic capacity, which means they can form new vessels. When the plaque is disrupted, the clot formation is triggered resulting in the reduction of oxygen supply. Possibly, BOECs might create a bypass due to his vasculogenic properties. Overall, the research was primarily designed for non-coding RNAs screening via microarray platforms in patients and their healthy relatives to establish certain non-coding RNAs as biomarkers.

You recently published a protocol in Nature on the establishment of outgrowth endothelial cells from peripheral blood. Could you tell us why this is important for our health?
The protocol is about how to isolate BOECs. Later on, we isolate the non-coding RNAs from these BOECs for further analysis. And as I said before, BOECs are important because of their angiogenic capacity; they are able to form new vessels. We think that in the case of the plaque formation, this bypass may really help to overcome the oxygen shortage. It might be that those subjects, who have a cardiovascular problem, may be due to the fact they have BOECs that are not functionally optimal.

What happens when BOECs don’t work properly?
We speculate that perhaps people, who present a decreased amount of BOECs, might be at a higher risk of developing cardiovascular diseases. In other words, fewer BOECs might mean higher chances to develop CVD symptoms derived from the plaque, such as ischemia and myocardial infarctions. So they might play a really important role.

BOEC colony advanced stage

BOEC colony advanced stage

What are the most important lines of research/approaches that have developed in your field over the past 5 or 10 years?
One important issue that has been recently achieved is the proper determination and classification of BOECs, taking into account that previously reasonable confusion was present in this area. For instance, Medina et al. have nicely characterized BOECs by considering molecular, proteomic and genetic approaches. In my opinion, the paper was really interesting to finally determine the nature of BOECs. Before, we can read in literature that sometimes certain cells were designed as BOECs when in reality were not such.

Was this finding also a start for a lot of other research?
Rather than a start, I think it was in this case a confirmation. Another person that has been working hard on BOECs and also has been doing therapeutic models, for instance, is Dr. Robert Hebbel. He is also an important reference to be mentioned in the field of angiogenesis and endothelial cells, including BOECs. He and his group have been even able to isolate BOECs from mice, cows, horses and all different animals. I think it is also relevant to be able to test some therapeutic approaches for example in murine models.

What is, according to you, the biggest challenge in current research in your field?
Let’s see, the biggest challenge? One important challenge would be to see the differences between patients and their relatives by microarray platforms and being capable to observe on and off events between them. And to discover which non-coding RNAs are the ones that are related to the plaque formation or angiogenesis, or which ones are down- or up-regulated in the patient. Also, I think it would be interesting if we find non-coding RNAs that are family orientated. It might be that there is a non-coding RNA that is common in that family but not in the others. That would also be very interesting.
Furthermore, when you do a CT scan for calcium deposition in the presumed healthy relative controls, you can observe that there are some relatives that present a high score. This calcium deposition is strongly linked with the future possibility of plaque forming. It would be also very interesting to check some differences in those individuals that might soon develop a cardiovascular event. That is also a big challenge; to use non-coding RNAs apart as a predictive tool.

Do you know if this is already been tested by research groups?
Some groups have seen a relationship between number of certain cells and CVD. But it turned out not to be related with real BOECs. Besides, different non-coding RNAs that are directly related with heart failure have been described.

Why does your line of research matter? Why should people put money into it?
I think translational research brings generally a better life to people, as for instance the fact of using non-coding RNAs as a predictive tool. Right now, we are using the CT scanning that is not 100% accurate. So, having different tests would be fantastic to more accurate diagnostics, for example. It is already known that biomedical and translational research improves the lifespan of people, more concretely in our case to prevent and better define CVD. Also, this kind of research provides us a better knowledge of the mechanism of BOECs in angiogenesis and the cardiovascular system, as an interesting challenge. Especially since in Western-Europe it is a top cause of mortality. Therefore, I think it is pretty clear why this topic is important.

Who or what will benefit from your research?
I think society in general will benefit due to the knowledge you create with it. Moreover, in the future when this technique would manage to become an accurate predictive tool; people, who present a high predisposition to develop CVD, will in fact benefit from it.

How does your research suit Sanquin?
The cells that we are studying are endothelial cells from the peripheral blood. So, I think this fact shows a very strong connection. The research is also related to angiogenesis, vessels, blood and at a certain point the CVD and heart failure which are also related to the blood itself. Summing up, there is a link among blood cells, vasculogenesis and the potential that those cells possess. Just bare in mind that those cells are very potent in terms of creating new vessels.

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