Noticias

The Government of Navarra highlights the donation to Navarrabiomed - FMS for the promotion of public research

Author
Gobierno de Navarra
  • Recognition to 78 people who have donated valuable objects to the Regional Community during 2022
  • President Chivite was grateful for the "decision to transfer part of your history to the whole citizenship”

The President of Navarra, María Chivite, chaired this afternoon the awards ceremony in honour of the people who have donated valuable objects to the Regional Community during the year 2022, thanking them for their “decision to transfer part of your history to the whole citizenship”. During her speech, the President highlighted a “especially significant" financial donation received by the Miguel Servet Foundation, the body that manages the Navarrabiomed biomedical research centre. Specifically, someone has donated his entire estate at death, estimated at half a million euros.

A total of 78 people have made donations to Navarra this year of objects of historical value intended for its museums and archives, as well as other significant assets. The awards ceremony, which took place in the Throne Room of the Palace of Navarra, was attended, in addition to President Chivite, by the Minister of Economy and Finance, Elma Saiz; the Minister of Culture and Sport, Rebeca Esnaola, and representatives of the honourees. The donors have received a diploma from the President, with which the Government of Navarra publicly thanks their contribution.
 
About half a million euros for research

During her speech, Chivite expressed her sincere gratitude to the person who donated his estate to the Miguel Servet Foundation for contributing “to the development of health research". "Private donations like this are an extra way of financing public biomedical research, which has increased its resources in this legislature and whose results make us all especially proud of this other heritage, knowledge, just as important as the material heritage”, she said.
It is noted that those wishing to collaborate with the activity developed by Navarrabiomed - Miguel Servet Foundation by making a donation, can complete this form or get in touch with the administrative team  from the centre. In both cases, information will be provided for the process to be followed for both individuals and companies.
•    See the complete information on the website of the Government of Navarra.

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La Presidenta Chivite con varias de las personas que han donado objetos la Comunidad Foral.
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Propuesta de adjudicación de la Ayuda para la intensificación de un/una F.E.A. del Servicio de Hematología y Hemoterapia del HUN para la Sala Blanca CellMa

Author
Navarrabiomed

La Unidad de Gestión de Navarrabiomed ha difundido hoy martes, 25 de abril, la propuesta de adjudicación de la "Ayuda para la intensificación de un/una F.E.A. del Servicio de Hematología y Hemoterapia del HUN para la Sala Blanca CellMa" 2023. El objeto de esta convocatoria de intensificación es incentivar, promover y consolidar el desarrollo de la actividad de la Sala Blanca CellMa en colaboración con el Hospital Universitario de Navarra.

A continuación, se facilita la documentación para su consulta y descarga. 

 

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25/04/2023 Propuesta de adjudicación
Adjudicación ayuda para la intensificación F.E.A. - Servicio de Hematología y Hemoterapia del HUN. Sala Blanca CellMa 2023
25/04/2023 Relación provisional y definitiva
Relación provisional y definitiva para la intensificación F.E.A. - Servicio de Hematología y Hemoterapia del HUN. Sala Blanca CellMa 2023
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The HUN and Navarrabiomed publish the findings of the first clinical trial in Spain with anakinra in COVID-19

Author
Navarrabiomed

This randomised study shows that the drug reduces the mean stay of patients in the ICU and produces a radiological improvement in COVID-19-related pneumonia.



This multicentre clinical trial, which was sponsored and led by Navarrabiomed – Fundación Miguel Servet and conducted between April 2020 and October 2021, has allowed the safety and efficacy of the anti-inflammatory and antirheumatic drug anakinra to be evaluated for the treatment of severe cases of COVID-19. The international journal Jama Network Open has published the results, which show that anakinra does not result in significant improvement with respect to conventional treatment in very serious cases as it does not avoid the need for mechanical ventilation or reduce the comparative mortality. 

However, use of the drug reduces the mean stay of patients admitted to the ICU and produces a radiological improvement in COVID-19-related pneumonia. Moreover, it appears to be more effective in less severe cases as significant improvements are seen in this group of patients. 

The patient sample comprised 179 adults diagnosed with severe COVID-19 and a mean age of 60.5 years. Patients were enrolled at 12 hospitals from seven Autonomous Communities. Thirty six of the 179 patients enrolled in the trial were recruited at the Hospital Universitario de Navarra, with ages ranging from 38 to 81 years. None of these patients suffered any relevant adverse event.

Hospitals involved and funding

The national coordinating investigator for the study was Dr. Patricia Fanlo Mateo, an Internal Medicine consultant at the HUN, who, together with the Clinical Trials team at Navarrabiomed and supported by the Methodology Service, was able to launch and conduct the trial during the pandemic, including seeking the authorisations required and analysing the final results.

The trial was funded by way of COVID-19 projects from the Government of Navarra, which allowed the conduct of studies into coronavirus during the pandemic. 

The participating hospitals were: the Complejo Hospitalario Universitario de Santiago, Hospital Álvaro Cunqueiro (Vigo), Hospital Universitario Son Espases (Palma de Mallorca), Hospital Universitario y Politécnico La Fe (Valencia), Hospital Universitario Vall d’Hebron and Hospital Clínic (Barcelona), Hospital Universitario La Paz and Hospital Ramón y Cajal (Madrid), Hospital Clínico Universitario Lozano Blesa and Hospital Miguel Servet (Zaragoza), Hospital Universitario de Cabueñes (Gijón) and the Hospital Universitario de Navarra. The trial was also supported by the Spanish Society for Internal Medicine (SEMI)’s Systemic Autoimmune Diseases Group (GEAS).

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De izda. a dcha.: Eva Zalba (EECC NB), Berta Ibéñez (Metodología NB), Patricia Fanlo (Medicina Interna HUN) y Ruth García (EECC NB).
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Mikel Izquierdo, recognised with the VII SER Navarra Award in the research category

Author
Navarrabiomed

Mikel Izquierdo, Principal Investigator of the Physical Exercise, Health and Quality of Life Unit (E-FIT) of Navarrabiomed and professor of the UPNA, was awarded yesterday at the VII SER Navarra Awards in the research category. Cadena SER Navarra recognised a total of 10 people or groups for their work in different areas of Navarra society at a ceremony held at the Baluarte Auditorium and presented by the journalists, Mamen García and Joaquim Torrents. 

In this 2023 edition, the pharmaceutical company Cinfa sponsored the research award and Alicia López de Ocáriz was the Corporate Medical Director, in charge of presenting the award that recognises the trajectory in numerous research projects in the field of Biomechanics and the Neuromuscular System with special emphasis on the effects of muscle strength training in different sports, aging and muscle performance. 

During his speech, Mikel Izquierdo thanked the radio station and the sponsor for the award and put the focus on a pandemic that existed before COVID-19: “Today, the pandemic of physical inactivity and sedentary lifestyle still persists, which causes 10 million deaths a year, 7 million myocardial infarctions and a total impact of 250 million dollars annually.” To reverse this situation, he stressed the importance of continuous physical exercise to achieve a higher quality of life. "Physical exercise should be done chronically throughout life. Currently we don't do enough, either in terms of quantity or intensity, and we must be aware that it is necessary to survive," he said during his speech. 

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VII Premios SER Navarra
Mikel
Izquierdo Redín
Head of the Unit

Propuesta de adjudicación de las ayudas predoctoral y postdoctoral Navarrabiomed 2022 y puntuaciones finales de las y los solicitantes evaluados

Author
Navarrabiomed

La Unidad de Gestión de Navarrabiomed ha publicado hoy miércoles, 8 de febrero la propuesta de adjudicación de las ayudas predoctoral y postdoctoral Navarrabiomed 2022 así como las puntuaciones finales de las y los solicitantes evaluados para cada una de las convocatorias: ayuda predoctoral y ayuda postdoctoral. Puede consultar y descargar a continuación la documentación correspondiente.

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08/02/2023 Propuesta de adjudicación
Adjudicación de ayuda postdoctoral Navarrabiomed 2022
08/02/2023 Propuesta de adjudicación
Puntuaciones finales programa de ayuda postdoctoral Navarrabiomed 2022
23/12/2023 Propuesta de adjudicación
Adjudicación de ayuda predoctoral Navarrabiomed 2022

Vanessa Arrieta will present her doctoral thesis on Monday, November 28

Author
Navarrabiomed
  • Vanessa Arrieta Paniagua, predoctoral researcher at the Translational Cardiology Unit of Navarrabiomed - IdiSNA will present her doctoral thesis by the Public University of Navarra next Monday, November 28, at 12:00, in the Assembly Hall of Navarrabiomed. 

The doctoral work, entitled "Role of sST2 in myocardial fibrosis in severe aortic stenosis”, has been developed at the University Hospital of Navarra and Navarrabiomed under the direction of Natalia López Andrés, Principal investigator of the Translational Cardiology Unit.

Aortic stenosis is the most common valvular heart disease in Europe and North America affecting 2-7%, depending on the region, in population over 65 years of age. To date, there is no medical treatment that can slow down or reverse the evolution of the disease, so aortic valve replacement (surgical or percutaneous) is the only treatment when symptoms or ventricular dysfunction appear.

This disease produces an abnormal progressive narrowing of the aortic valve that, as a result of pressure overload, causes hypertrophy of the left ventricle. In this process, myocardial fibrosis has an important pathophysiological role, as well as a prognostic role. Initially, myocardial fibrosis is part of a compensatory mechanism, but in advanced stages a focal replacement fibrosis appears, leading to ventricular dysfunction and heart failure. The pathophysiological mechanisms underlying these processes are not fully understood. 

Focal replacement fibrosis can be detected and quantified by cardiac magnetic resonance imaging (MRI) with the delayed enhancement (DE) sequences. The presence of DE in patients with severe aortic stenosis has been shown to be an independent predictor of mortality and unfavourable clinical outcome in this group of patients. However, MRI is an expensive technique with limited availability, so it is not used in the follow-up of this group of patients in routine clinical practice.

The hypothesis of this thesis is that as the levels of soluble ST2 (sST2), a biomarker associated with the process of fibrosis and myocardial remodelling, are elevated in case of aortic stenosis, they may have a prognostic value. Specifically, this study addresses the role of sST2 in myocardial fibrosis in severe aortic stenosis. 
 

Research development 

The work is proposed from a translational point of view, and has a dual goal. First of all, to delve into the pathophysiological role of tSS2 in severe aortic stenosis. To this end, a proteomic study has been carried out to assess the proteins modulated by sST2 in human cardiac fibroblasts and the in vitro effects of sST2 on human cardiac fibroblasts have been investigated. The results have been validated in vitro in a rat model with pressure overload and in myocardial biopsies of patients with aortic stenosis that underwent surgery. 

Likewise, it has been demonstrated that sST2 exerts a deleterious role in human cardiac fibroblasts, on the one hand, affecting the mitochondrial function of the cell and thus increasing oxidative stress and the synthesis of proinflammatory molecules and on the other hand, promoting differentiation to myofibroblasts and increasing the synthesis of profibrotic molecules. These findings were validated in the animal model and in myocardial biopsies of patients with aortic stenosis.

Secondly, from the clinical point of view, a cohort of patients with severe aortic stenosis with surgical indication was analysed to check if the blood levels of sST2 are associated with the DE evaluated by MRI in patients with severe aortic stenosis. Thus, it is observed that patients with severe aortic stenosis with cardiac MRI DE have significantly higher blood levels of sST2 than those without RT. Blood sST2 levels are positively correlated with DE mass and with VI mass in patients with severe aortic stenosis. High levels of sST2 make it possible to identify patients with severe aortic stenosis with DE, without having to perform cardiac MRI, in a simple way that can be applied in routine clinical practice.
 

Dissemination of results 

The work carried out has led to several scientific publications: in 2019, in the journal Clinical Science, “Soluble ST2 promotes oxidative stress and inflammation in cardiac fibroblasts: an in vitro and in vivo study in aortic stenosis”, and in 2020 in the journal Cells, “Soluble St2 Induces Cardiac Fibroblast Activation and Collagen Synthesis via Neuropilin-1”.   

In addition, the results have been disclosed at several national and international congresses such as the SEC Congress in Bilbao (in 2015 and in 2017), at the 29th EACTS Annual Meeting in Amsterdam, in 2015 or at the Heart Failure Congress in Paris, in 2017.

 

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Vanessa Arrieta Paniagua, investigadora predoctoral de la Unidad de Cardiología Traslacional de Navarrabiomed y Médica Adjunta en el servicio de Cardiología del Hospital Universitario de Navarra
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The Government of Navarra launches the Navarra Association for Hemp Research

Author
Gobierno de Navarra
  • Navarrabiomed participates together with the Department of Rural Development and Environment, the UPNA, CSIC-IDAB and the public companies INTIA and Nasertic and the company Josenea


The Government of Navarra has approved at this Wednesday's session its initiative to join the Navarra Association for Hemp Research (ANIC), promoted by the Department of Rural Development and Environment and that will be established shortly together with the UPNA (and its two institutes, ISFOOD-Institute for Innovation and Sustainable Development of the Food Chain- and IMAB -Institute for Multidisciplinary Research in Applied Biology), Navarrabiomed (biomedical research centre), the CSIC-IDAB (Institute of Agrobiotechnology of the Higher Scientific Research Centre), the public companies INTIA and Nasertic and the private company Josenea.

The purpose of the Association is to obtain and manage, with a criterion of equity between the partners and with a territorial vision for Navarra, the relevant licenses or authorizations of the Spanish Agency for Medicines and Health Products (AEMPS) and, specifically, the authorization for the cultivation of hemp plants for research purposes; the authorization for the cultivation of these plants for medical and scientific purposes; and, subsequently and on an annual basis, the annual authorization of total area and plots for the cultivation of hemp plants.


In addition, the objectives of the ANIC are:

  • To group and coordinate all those operating with industrial or medicinal hemp in Navarra, at present or in the future, providing them with a legal tool for coordination and sectoral dialogue for their institutional and intersectoral relations.
  • To promote cooperation between companies, research and training centres and institutions for the boosting, growth and coordination of the industrial and medicinal hemp sector in Navarra, in its aspects of research, cultivation, industrial transformation and marketing of final product, encouraging the design and launch of collaborative projects.
  • To contribute to the promotion of research, development and innovation in the industrial and medicinal hemp sector of Navarra, in all links of the value chain, and with special emphasis on: the development of new varieties of industrial and medicinal hemp and genetic research; in the research of medical, pharmacological, food, industrial and cosmetic properties of hemp; in the research of medicinal, industrial and commercial applications of its derivatives; in the research of the economic potentials of industrial and medicinal hemp as an alternative crop for economically disadvantaged areas and/or in risk of depopulation; and any new line of research that may be interesting for the sector and the territory of the Autonomous Community of Navarra.
  • To create, consolidate and enhance a sectoral image for all the economic and research activity that is generated around industrial and medicinal hemp in Navarra, and that includes all aspects of research, agricultural, cultivation, industrial, biomedical and commercial aspects.
  • And, finally, to facilitate and coordinate sectoral relations at the national and international levels.
     

Gómez: "Navarra has great potential in the entire value chain”

After its approval in the Government session, the Minister of Rural Development and Environment, Itziar Gómez, has presented this initiative accompanied by representatives from the various centres, societies and the company that will be part of the Association. The minister stressed that "Navarra has great potential in the entire value chain: a strong agricultural sector, personnel and reference centres in research, as well as important pharmaceutical and agri-food companies”.

“Therefore, we believe that the Regional Community can be a reference and be well positioned for the new regulatory framework in the matter that is planned for 2023. Interestingly those who want to operate in this area in Navarra are well established at the starting line of a new economic sector that can thrive and for which Navarra, as said, has potential throughout the value chain,” she explained.

As the minister has pointed out, the Department “has been working on this issue since 2020. Early that year we commissioned a study on the potentialities of hemp cultivation as a strategic circular economy and innovation project for Navarra and from there we continued to take steps”.
On the one hand, we contacted the AEMPS (Spanish Agency for Medicines and Health Products), “who grants the licenses, to verify with them the real possibilities of promoting a project with a research license and, on the other hand, making an appeal to different agents that we understood might be interested in hemp research to design together a project to carry out,” she explained.

As explained by Itziar Gómez, “The truth is that we had a very good reception in terms of forming a working group to boost research. In addition to those now present, we also contacted pharmaceutical companies and other private companies that do not rule out participating in the Association at a later stage. In fact, the association is open to the incorporation of new partners”.

The current phase of the association, in addition to its own incorporation, focuses on submitting a research project to the AEMPS to obtain a research license, so, at this moment in the process, the objective is not commercial cultivation.
Once the association is formally constituted and once approved the proposed statutes in the Government Agreement record approved at today's session, the Autonomous Community of Navarra will belong to the association as sponsor or founder, participating in the act of incorporation of the association.


Research project

In parallel to the steps for the constitution of the Association, its members have worked on a first research project that they are finalizing to present to the AEMPS once the ANIC is set up.

This is a variety testing project. It consists of selecting hemp varieties with a high CBD content (a non-psychoactive component of hemp) and a low THC content (psychoactive component), adapted to the growing conditions of Navarra, taking into account morphological, physiological, agronomic (phenotypic in general) and genotypic characteristics (by using molecular markers indicating the THC/CBD chemotype ratio of the varieties).
In addition, a second objective is the study and characterization of the derived products for their marketing by industries of the agri-food sector as proteins and lipids of nutritional interest and biocompounds from the selected varieties.

The project would be located on the Josenea de Lumbier farm that meets the prerequisites set by the AEMPS, that is, it is located in a closed, video-monitored environment, near a population centre and a police station or civil guard station.



Photo caption L-R: Ignacio Gil (General Directorate of Agriculture and Livestock); Luis Orcaray (INTIA); Maite Mendioroz (Navarrabiomed); Txus Cía (Josenea); Lucía Ramírez (IMAB-UPNA); Gonzalo Rodríguez (NASERTIC); Itziar Gómez (minister); José María González de Diego (CSIC-IDAB); Natxo Irigoien (UPNA); and Patxi Ibáñez (ISFOOD-UPNA) .

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La consejera Gómez con representantes de las entidades que forman la Asociación Navarra para la Investigación del Cáñamo.
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Carmen Gómez will present her doctoral thesis on Tuesday, July 5th

Author
Navarrabiomed

Carmen Gómez Arrebola, predoctoral researcher at the Microbial Pathogenesis Research Unit of Navarrabiomed, will be sitting her viva (Public University of Navarra) next Tuesday, July 5th at 11:30 in the examination hall of EDONA, Edificio El Sario (UPNA).


The doctoral work, entitled "Role of the two-component systems of Staphylococcus aureus in the susceptibility to complestatin and corbomycin and in gene regulation in the absence of phosphorylation”, has been developed at Navarrabiomed under the direction of Dr. Iñigo Lasa Uzcudun and Dra. Cristina Solano Goñi.

Staphylococcus aureus (S. aureus) is a versatile bacterium that can be found as a commensal on the skin of approximately 30% of the population without causing any problems. However, when it crosses the epithelial barrier and depending on the carrier's immune status, it can cause mild pathologies, such as abscesses, or severe ones, such as endocarditis or osteomyelitis. There is a wide range of drugs for the treatment of these pathologies, however, S. aureus has developed mechanisms that allow it to increase its resistance and evade the effect of these antibiotics. 

Bacteria have the ability to adapt to the changes that occur around them thanks to different detection and communication systems, including the so-called “two-component systems” (TCSs). Through them, the bacteria perceive what is happening around them and by modulating the expression of certain genes, can adapt to the changes occurred. The TCSs of S. aureus they have a very important role in the development of resistance to the various antimicrobials currently used in the clinical setting, as well as in the stimulation of growth in the form of biofilm, further increasing their resistance to antibiotics.
The appearance of strains of multidrug-resistant S. aureus has led to the alarming need to develop new antibiotics that allow the treatment of infections caused by these strains, as well as the need for progress in our knowledge on the molecular mechanisms that produce this increased resistance. 


Thesis abstract and results

During her doctoral thesis, Carmen Gómez has analysed the involvement of the TCSs of S. aureus in the susceptibility to two antibiotics of the glycopeptide family, complestatin and corbomycin, recently discovered. The results have shown that the VraSR system regulates elements of the bacterial wall that affect the susceptibility of this bacterium to both antibiotics. 

Another part of the study has been devoted to analyse the regulation by TCSs in their non-phosphorylated form. It has traditionally been considered that the response regulators of TCSs exercise their regulatory function in their phosphorylated state, and that in their non-phosphorylated state, they have no regulatory activity. However, considerable evidence shows that TCSs in their unphosphorylated state also exert gene expression modulation functions. After a review of the existing evidence regarding the regulation by TCSs in their non-phosphorylated state, the work has delved into the regulation of biofilm formation by ArlRS TCS. The results obtained suggest that ArlR regulates the expression of the main exopolysaccharide of the S. aureus biofilm in both its phosphorylated and non-phosphorylated state. 


Disclosure and financing

The work carried out has led to the scientific publication, “Regulation of gene expression by non-phosphorylated response regulators”, published in International Microbiology. A second publication entitled “Staphylococcus aureus susceptibility to corbomycin and complestatin depends on the VraSR two component system” has been submitted and is in the process of being reviewed. 

In addition, it has been disseminated at the 31st European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) and the XXVIII Congress of the Spanish Society of Microbiology.
For the development of the thesis, Carmen Gómez had a predoctoral contract from the UPNA. Research has received funding through the calls for Aid to R&D&i projects 2017 of the Ministry of Economy, Industry and Competitiveness and Aid to R&D&i projects 2020 of the Ministry of Science and Innovation, granted to the projects:

  • “Functional characterization of the molecular determinants for the adaptation of Staphylococcus aureus to virulence”.  BIO2017-83035-R. 
  • “Non-contiguous operons: a new level of gene regulation in bacteria”. PID2020-113494RB-100. 
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A HUN and Navarrabiomed project, recognized in the IdiSNA FTyS Intramural Awards Call

Author
Navarrabiomed

The prize, with 10,000 euros, has been awarded ex aequo to a study on brain magnetic resonance imaging as a biomarker of ALS, developed by the University Hospital of Navarra in collaboration with Navarrabiomed, and an application designed by the University Clinic of Navarra to monitor the treatment of food allergies with oral immunotherapy.
 

The Scientific Directorate of IdiSNA has decided to grant the Technology and Health Foundation (FTyS) award ex aequo, with 10,000 euros, to two projects related to health technologies. The different entities that make up IdiSNA were able to apply for this award through an intramural call.
Dr. Teresa Cabada, Head of the Neuroradiology Section of the University Hospital of Navarra, leads one of the winning proposals. A study on brain magnetic resonance as a biomarker in degenerative motor neuron disease. As described by Cabada, “Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease whose diagnosis is difficult at an early stage, which translates into a delayed diagnosis and delayed administration of neuroprotective drugs”. All this highlights the importance of defining diagnostic and prognostic biomarkers in ALS.

To date, 33 patients have been recruited who have undergone a clinical and neuropsychological evaluation. The post-processing of the MRI is carried out by the Algebra and Applications Research Unit of Navarrabiomed, which analyses the images along with other clinical variables to find radiological markers associated with the disease or its evolution. "By using advanced sequencing techniques, mathematicians are able to detect subtle alterations and generate predictive models from the data obtained”, it concludes.

With this project, funded by the Government of Navarra and which now also has financial support from IdiSNA, magnetic resonance imaging is postulated as a promising test to predict the disease and its evolution.
The second acknowledgement has been awarded to an initiative of the University of Navarra Clinic. It is an application to monitor the treatment of food allergies with oral immunotherapy led by Dr. María José Goikoetxea, specialist of the Department of Allergology.

 

Caption (from left to right): Itiziar Uzqueda (Navarrabiomed), Marisol Gómez (Navarrabiomed), Javier Díaz (HUN), Ivonne Jericó (HUN), Juan Quizhpilema (HUN) Teresa Cabada (HUN), José Manuel Hidalgo (HUN), María José Goikoetxea (CUN), Sergio Sánchez (CUN), Maite Lacunza (CUN) and Amaia Izal ( CUN). 

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Research by Navarrabiomed and the HUN identifies sex-specific differences in the valves of patients with aortic stenosis

Author
Navarrabiomed

These findings show differences between men and women in the triggering mechanisms of the disease and open the door to the study of specific therapeutic targets that make personalized patient treatment possible.
 

Cardiovascular diseases are the main cause of mortality and disability worldwide and represent an increasing health expenditure due to the aging of the population. Specifically, severe degenerative or calcified aortic stenosis (CAD) is the most common form of heart valve disease, a narrowing that occurs in the valve and leads to its calcification and degeneration. Currently, there is no effective pharmacological treatment that alters the evolution of the disease, with aortic valve replacement surgery being the only way to improve symptoms and long-term survival.

The prevalence of CAD is estimated at around to 3.4% in patients over 75 years of age, and it increases noticeably with age. It is estimated that in Spain there are about 145,469 people with CAD only accounting for the group over 75 years old1.
With the aim of slowing down the evolution of the disease and avoid surgery, in 2016 the Navarra Biomedical Research Centre (Navarrabiomed) and the University Hospital of Navarra (HUN) began a study on mechanisms involved in the development of this pathology. The results of this research, published in Frontiers in Cardiovascular Medicine, conclude that the triggering factors of aortic valve disease are different in men and women and, therefore, open the door to personalized medicine through the study of sex-specific therapeutic targets that enable individualized patient treatment.


The authors of the work are Natalia López-Andrés, Principal Investigator of the Translational Cardiology Unit of Navarrabiomed; Lara Matilla, Mattie Garaikoetxea, Amaya Fernández-Celis, Alicia Gainza y Eva Jover, all researchers in this unit. On behalf of the HUN, the team includes Vanessa Arrieta, Amaia García-Peña and Adela Navarro, cardiologists of the Heart Area; Virginia Álvarez, Head of the Heart Area, and Rafael Sádaba, cardiac surgeon.  


Research with a gender dimension

Clinical studies prior to this one show that the valves of men and women are different, but then the causes and implications of those differences were not well known. For a same degree of severity of CAD, women have a lower degree of calcification and greater valve fibrosis than men. In addition, CAD is associated with other important diseases that aggravate the patient's prognosis, such as diabetes and chronic renal failure.
This information was decisive for considering the gender dimension in the project: “we confirmed the results that had been found in clinical trials analysing valves donated by patients undergoing surgery at the HUN whereby there was an increased calcified tissue in men compared to women”, explains Dr. López-Andrés, Principal Investigator of the Translational Cardiology Unit of Navarrabiomed, who stresses on the generosity of these people for donating their tissues for research and thus perhaps preventing other people from undergoing an intervention in the future. “We believe that if the aortic valves at the final stage, before surgery, seem different at a clinical level, perhaps they could also be different at a molecular and cellular level. And, indeed, they are.”


Study characteristics

The research has been developed between 2016 and 2021 financed by the Carlos III Health Institute in two Calls of the Health Research Fund (FIS) and has characterized for the first time sex-related cellular and molecular mechanisms of markers that cause valve damage and that lead to the onset of disease and valve replacement.
For this, a total of 238 patients with severe aortic stenosis referred to the HUN for surgical replacement of the aortic valve from June 2013 to October 2020 were recruited. Of those 238, 39.1% were women, an expected fact since women suffer less from aortic stenosis than men and also at an older age: specifically, the average is 77 years compared to 73 years in men. According to Dr. Natalia López-Andrés, "the analyses performed also confirm that the aortic valves of the women were in a better condition than those of the men.”


Personalized medicine: the patient-tailored approach

The research results suggest that the mechanisms involved in aortic disease are different in men and women, by providing new molecular and cellular knowledge for the development of sex-specific strategies aimed at differential disease-provoking processes that contribute to aortic stenosis.
The aortic valve tissue of women presented less calcification, inflammation, oxidative stress, apoptosis and improved remodelling of the extracellular matrix. Therefore, this is radically different from the tissue of men, which is much more calcified. These findings suggest that pharmacological treatments designed to slow the progression of the disease should be different. “If the valves are different, it is because the mechanisms that have triggered the disease are also different. If we intend to treat this disease at the origin so that the valve does not deteriorate and need not be replaced, the pharmacology to be used will also be different. We cannot look for a single treatment for everyone, because it may not be effective,” emphasizes Dr. López-Andrés. The results of this study have been presented in the Congress of the Heart Valve Society held in Miami between March 2 and 5, 2022. In addition, the research conducted by Dr. Natalia López-Andrés has been awarded best report in the categories of "Basic science” and "Aortic valve" at this congress for the progress made by research in aortic stenosis.
The next phase, which has already received financing by the Department of Health of the Government of Navarra, will focus on the search for pharmacological treatments that can block the onset of these differences and the development and progression of two very important associated diseases such as diabetes and chronic kidney damage, opening up new possibilities for the therapeutic management of these patients.
Overall, the research results show the importance of considering the gender dimension as a potential experimental variable to be taken into account when studying new therapeutic approaches that open the door to the development of more effective, specific and individualized treatments for patients.
 
_______________
  1 Source: European Society of Cardiology
 

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