When I was a child, and as my family knows, I used to get hold of plastic cups, dry beans and a little wet cotton and put them at the window, waiting for them to grow – some were more exposed to the sun, others were more protected. Weeks later, I used to look at the results, since the different conditions led to different bean plants: some were bigger and healthier while others were less developed because they had fewer conditions to grow. I did the same with chickpeas, garlic, parsley, among others – in fact, I experimented with everything that had the potential to grow under my command.

Years went by, I grew up, and these experiments stayed only in my memory. Still, in a project I conducted in high school, I succeeded in having some of this work done at a microbiology laboratory (at the Catholic University in Caldas da Rainha), involving simple experiments, which, at that stage of my academic path, were something new and quite motivating. My group wanted to know how an “Ideal Hospital” would be like, and hygiene and the control of hospital infections could not be neglected. Accordingly, we conducted several experiments in which our hands were the source of various bacterial cultures subject to different conditions. The desire to know more through “experience” continued to manifest itself. A year later, I was admitted to this faculty and the hard work began.

Here I felt, somehow, that I had to yield to research done by others. I do not mean yield as if this was a dictatorship, quite the opposite. The reason why I say so is that since then my role in this faculty has largely consisted of studying, with the time it involves, learning the evidence built up over hundreds of years by thousands of people who spent their time, careers and lives finding something new, trying to understand “why”. In those days I lacked the scientific bases that allowed me to address some sort of challenge. I focused on my studies and I waited.

I saw year 5 as “the opportunity”, since I had already completed my basic years of training, had clinical practice and had to present, in the following year, the master degree final project. “This is the moment” – I thought to myself. I have always been interested in the field of Rheumatology, not so much the clinical component itself, but the pathology – the mechanisms that lie behind diseases. After contacting Professor João Eurico Fonseca and having a meeting with Professor Helena Canhão, who informed me about some of the projects underway at the Rheumatology Research Unit (UIR) and at the Institute of Molecular Medicine (IMM), I decided to participate in a project that aimed to study the relationship between atherosclerosis and bone remodelling and identify mechanisms common to both, contributing to the identification of new biomarkers and potential therapeutic targets of vascular and bone diseases. This work was done in the context of the PhD thesis of Diana Fernandes, MSc. After discussing it with my supervisor Professor Maria José Santos, I decided to focus on a more specific mechanism, given several obvious limitations of knowledge, time, and resources. So I studied vitamin D as the core topic of my work. I was most welcome by the entire UIR team, and I take this opportunity to express my thanks to them. I admit I was a bit anxious about participating in such a project, as I feared everything, mostly the fact I did not know anybody or how a laboratory worked. I was never short of support, and that was a big help in the beginning, when I was still adjusting to the challenge I had chosen to face. Then came the project named “Vitamin D in patients with atherosclerosis – is there a link between atherosclerosis and bone mass?”, which was subsequently submitted to the 16th programme “Education through Science”, accepted and funded by the Calouste Gulbenkian Foundation/FMUL

Vitamin D is an important player in bone metabolism. However, this protein has been attributed new functions, namely in protecting the cardiovascular system and in the physiopathology of autoimmune diseases, type 2 diabetes mellitus and obesity. One way by which it is believed that vitamin D protects the cardiovascular system is atherogenesis, where the role of this vitamin is not yet fully understood. It is thought that this beneficial effect occurs by inhibiting vascular calcification by blocking the production of inflammatory cytokines and adhesion molecules. There is evidence that low vitamin D levels are associated with greater thickness of atheromatous plaques and IMT (intima-media thickness) in the carotid, although this does not occur in other studies. Improvement in arterial stiffness in patients who were administered a vitamin D supplement compared to the placebo group has also been demonstrated, as well as the involvement of vitamin D in the renin-angiotensin-aldosterone system (RAAS), in immune system regulation and in the interference of the cardiac muscle, resulting indirectly in cardiac morbidity and mortality. Calcitrol, the active form of vitamin D, is a negative regulator of renin, interfering in the RAAS and limiting the production of angiotensin II, an inflammatory and atherogenic cytokine involved in the development of atherosclerotic plaques in apoE-/- mice. Also in this same animal model of atherosclerosis, treatment with low doses of calcitrol significantly decreased the blood pressure values and the progression of atherosclerotic plaques in the Valsava sinuses, thus suggesting a possible importance of blood pressure as a mediator between vitamin D and atherosclerosis.

Epidemiological studies have shown a correlation between the prevalence of osteoporosis and atherosclerosis, regardless of age, body mass index and other cardiovascular risk factors, suggesting the presence of common underlying mechanisms. My hypothesis is that vitamin D may be a link between these two pathologies. Accordingly, this work aims to identify the relationship between the serum levels of vitamin D, atherosclerosis and bone mass. The importance of blood pressure and of inflammation as mediators in the relationship between vitamin D and atherogenesis will also be studied.

With regard to practice, patients who undergo endarterectomy in the Vascular Surgery Department of CHNL – Santa Maria Hospital have been included in this study. Along with Sofia Barreira and António Nicolau Fernandes, my classmates also involved in the same core project, we have applied the clinical protocol to patients, thus collecting the necessary information and values after obtaining their informed consent. This is where the project gives me “more enjoyment” – pardon me for the expression – when I see the information and data increasing. This is after we have talked to patients, spent time and had concerns that reflect in the data collection in order to subsequently analyse, reflect and draw conclusions.

I have hypotheses, but I do not know if the results will be similar, given that there are many factors that influence them. However, I believe that the most important, in addition to understanding why I have obtained them or not, is to have learned the “method” that any scientific work requires, to have experienced true rigour, to have understood what “research” really is, and to have been involved in it, particularly translational and clinical research. This is what I want to take with me for my future profession, which is getting closer: the notion that medical practice is possible thanks to a lot of the practical work that can support it, and above all the willingness to continue to participate actively in projects that aim to advance science and medical education.

The bean plants may have yielded just a few beans at the time, but they produced a fruit which, in my view, is the corollary of the whole story: the will to always experiment and find something new. None of this would have been possible without the support of GAPIC and the Calouste Gulbenkian Foundation/FMUL scholarship. I strongly advise all those who have the opportunity to conduct some sort of research work, whether clinical or in a lab, not to waist it, as they will emerge much richer, with a more solid view of the academic world, more skilled, and better professionals.

 

Pedro Oliveira Santos
psantos1@campus.ul.pt