Vascular Pathophysiology

Vascular Pathophysiology

Vascular Pathophysiology

 

Principal investigator: Maria Eugenia Gonzalez Barderas, MD.
E-mail: megonzalezb@sescam.jccm.es

 

Currently, the central topic of our research activity is the study of molecules involved in physiopathological mechanisms of several diseases, mainly cardiovascular (CV) diseases, through –OMICS tools, among others molecular biology techniques.

 

Nowadays, CV diseases are the leading cause of death in developed countries and present high prevalence in developing countries. Moreover, CV risk factors (hypertension, hight cholesterol, diabetes, etc.) increase the chance of developing a CV disease in the future. For that reason, to improve prevention techniques, as well as early detection of these kinds of diseases, the research of the physiopathological connection between CV risk factors and CV diseases is crucial. To do this, we must study these pathologies from the “continuum CV”, which describes the progressive atherosclerotic process, which starts with the development of CV risk factors and ends with the death of the patient. This dead is due to a CV disease, after the development of organ damage or others clinical complications.

 

In this context, the research lines of our group cover different CV risk factors and CV diseases such as hypertension, degenerative aortic stenosis and atherosclerosis. In addition, we study other pathologies associated with these diseases such as Alzheimer's, psoriasis and progeria.

 

The methodologies employed are focus, on the one hand, to a simultaneous analysis of thousands of molecules present at a certain moment in cells, tissues or biological fluids, with the aim of identify molecular panels which are characteristics of risk or CV disease. On the other hand, to study the diagnostic potential, prognostic and/or therapeutic of the proteins of interest found in these panels using different in vitro and in vivo models.

 

 

Best publications in the last years

 

Pubmed: MG.Barderas

 

1. Corbacho-Alonso N, Sastre-Oliva T, Corros C, Tejerina T, Solis J, López-Almodovar LF, Padial LR, Mourino-Alvarez L*, Barderas MG*. PRIORITIZATION OF CANDIDATE BIOMARKERS FOR DEGENERATIVE AORTIC STENOSIS THROUGH A SYSTEMS BIOLOGY-BASED IN-SILICO APPROACH. J Pers Med. 2022 Apr 15;12(4):642. doi: 10.3390/jpm12040642.

 

2. Sastre-Oliva T#, Corbacho-Alonso N#, Albo-Escalona D, Lopez JA, Lopez-Almodovar LF, Vázquez J, Padial LR, Mourino-Alvarez L*, Barderas MG*. THE INFLUENCE OF CORONARY ARTERY DISEASE IN THE DEVELOPMENT OF AORTIC STENOSIS AND THE IMPORTANCE OF THE ALBUMIN REDOX STATE. Antioxidants (Basel). 2022 Feb 5;11(2):317. doi: 10.3390/antiox11020317.

 

3. Corbacho-Alonso N, Baldan-Martin M, Lopez JA, Rodriguez-Sanchez E, Martinez PJ, Mourino-Alvarez L, Sastre-Oliva T, Cabrera M, Calvo E, Padial LR, Vazquez J, Vivanco F, Alvarez-Llamas G, Ruiz-Hurtado G, Ruilope LM, Barderas MG. CARDIOVASCULAR RISK STRATIFICATION BASED ON OXIDATIVE STRESS FOR EARLY DETECTION OF PATHOLOGY. Antioxid Redox Signal. 2021 May 26. doi: 10.1089/ars.2020.8254.

 

4. González-Cantero A, Ortega-Quijano D, Álvarez-Díaz N, Ballester MA, Jimenez-Gomez N, Jaen P, González-Cantero J, González-Calvin JL, Barderas MG, Shin DB, Mehta NN, Gelfand JM. IMPACT OF BIOLOGICAL AGENTS ON IMAGING AND BIOMARKERS OF CARDIOVASCULAR DISEASE IN PATIENTS WITH PSORIASIS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED PLACEBO-CONTROLLED TRIALS. J Invest Dermatol. 2021 Apr 21:S0022-202X(21)01149-0. doi: 10.1016/j.jid.2021.03.024.

 

5. Martin-Rojas T, Sastre-Oliva T, Esclarín-Ruz A, Gil-Dones F, Mourino-Alvarez L, Corbacho-Alonso N, Moreno-Luna R, Hernandez-Fernandez G, Lopez JA, Oliviero A, Barderas MG. EFFECTS OF GROWTH HORMONE TREATMENT AND REHABILITATION IN INCOMPLETE CHRONIC TRAUMATIC SPINAL CORD INJURY: INSIGHT FROM PROTEOME ANALYSIS. J Pers Med. 2020 Oct 21;10(4):183. doi: 10.3390/jpm10040183.

 

6. Calvo E#, Corbacho-Alonso N#, Sastre-Oliva T, Nuñez E, Baena-Galan P, Hernandez-Fernandez G, Rodriguez-Cola M, Jimenez-Velasco I, Corrales FJ, Gambarrutta-Malfati C, Gutierrez-Henares F, Lopez-Dolado E, Gil-Agudo A*, Vazquez J*, Mourino-Alvarez L*, Barderas MG*. WHY DOES COVID-19 AFFECT PATIENTS WITH SPINAL CORD INJURY MILDER? A CASE-CONTROL STUDY: RESULTS FROM TWO OBSERVATIONAL COHORTS. J Pers Med. 2020 Oct 21;10(4):182. doi: 10.3390/jpm10040182.

 

7. Mourino-Alvarez L, Baldan-Martin M, Sastre-Oliva T, Martin-Lorenzo M, Maroto AS, Corbacho-Alonso N, Rincon R, Martin-Rojas T, Lopez-Almodovar LF, Alvarez-Llamas G, Vivanco F, Padial LR, de la Cuesta F, Barderas MG. A COMPREHENSIVE STUDY OF CALCIFIC AORTIC STENOSIS: FROM RABBIT TO HUMAN SAMPLES. Dis Model Mech. 2018 Jun 19;11(6). pii: dmm033423. doi: 10.1242/dmm.033423.

 

8. Mourino-Alvarez L, Baldan-Martin M, Gonzalez-Calero L, Martinez-Laborde C, Sastre-Oliva T, Moreno-Luna R, Lopez-Almodovar LF, Sanchez PL, Fernandez-Aviles F, Vivanco F, Padial LR, Akerstrom F, Alvarez-Llamas G, de la Cuesta F, Barderas MG. PATIENTS WITH CALCIFIC AORTIC STENOSIS EXHIBIT SYSTEMIC MOLECULAR EVIDENCE OF ISCHEMIA, ENHANCED COAGULATION, OXIDATIVE STRESS AND IMPAIRED CHOLESTEROL TRANSPORT. Int J Cardiol. 2016 Dec 15;225:99-106. doi: 10.1016/j.ijcard.2016.09.089.

 

9. Mourino-Alvarez L, Iloro I, de la Cuesta F, Azkargorta M, Sastre-Oliva T, Escobes I, Lopez-Almodovar LF, Sanchez PL, Urreta H, Fernandez-Aviles F, Pinto A, Padial LR, Akerström F, Elortza F, Barderas MG. MALDI-IMAGING MASS SPECTROMETRY: A STEP FORWARD IN THE ANATOMOPATHOLOGICAL CHARACTERIZATION OF STENOTIC AORTIC VALVE TISSUE. Sci Rep. 2016 Jun 3;6:27106. doi: 10.1038/srep27106.

 

10. Baldan-Martin M, Mourino-Alvarez L, Gonzalez-Calero L, Moreno-Luna R,Sastre-Oliva T, Ruiz-Hurtado G, Segura J, Lopez JA, Vazquez J, Vivanco F, Alvarez-Llamas G, Ruilope LM, de la Cuesta F, Barderas MG. PLASMA MOLECULAR SIGNATURES IN HYPERTENSIVE PATIENTS WITH RENIN-ANGIOTENSIN SYSTEM SUPPRESSION: NEW PREDICTORS OF RENAL DAMAGE AND DE NOVO ALBUMINURIA INDICATORS. Hypertension. 2016 Jul;68(1):157-66. doi: 10.1161/HYPERTENSIONAHA.116.07412.

 

 

 

Patents

 

- National Patent: METHOD FOR DIAGNOSIS, PROGNOSIS OR PREDICTION OF THE EVOLUTION OF AORTIC STENOSIS MÉTODO. Laura Mouriño Álvarez, Luis F López Almodóvar, Luis Rodríguez Padial, Nerea Corbacho Alonso, Tamara Sastre Oliva, Jorge Solís Martín, Cecilia Corros Vicente, María Eugenia González Barderas. Reference: P202130281 (2021)

 

- National Patent: DIAGNOSIS AND PROGNOSIS KIT FOR CHRONIC RENAL DISEASE IN HUMAN SUBJECTS. María Posada Ayala, María G. Barderas, Gloria Alvarez-Llamas, Fernando Vivanco Martinez. Reference: P201330663 (2013).

 

- European Patent: ALPHA-1-ANTICHYMOTRIPSYN: A DIAGNOSTIC AND PROGNOSTIC METHOD FOR THE EVALUATION OF AORTIC STENOSIS. Tatiana Martin-Rojas, Felix Gil-Dones, Verónica M. darde, Luis R. Padial, Maria G. Barderas et al. Reference: PCT/ES2011/070365 (2011).

 

- National Patent: ALPHA-1-ANTICHYMOTRIPSYN: A DIAGNOSTIC AND PROGNOSTIC METHOD FOR THE EVALUATION OF AORTIC STENOSIS. Tatiana Martin-Rojas, Felix Gil-Dones, Verónica M. darde, Luis R. Padial, Maria G. Barderas et al. Reference: P201030759 (2010).

 

 

 

 

Research team

 

Maria Eugenia G. Barderas: Lab chief. PhD in Biology, Universidad Complutense, Madrid (Spain)

 

Luis R. Padial: MD, Universidad de Granada (Spain).

 

Laura Mouriño Álvarez: Postdoctoral researcher; PhD. in Biochemistry, Universidad Complutense, Madrid (Spain).

 

Nerea Corbacho Alonso: Postdoctoral researcher; PhD. in Biochemistry, Universidad Complutense, Madrid (Spain). Predoctoral researcher; BSc. in Biology, Universidad Complutense, Madrid (Spain).

 

Tamara Sastre Oliva: Predoctoral researcher; Superior Laboratory Technician Diploma, Toledo (Spain); BSc. in Biology, Universidad Alcalá de Henares, Madrid (Spain).

 

Inés Perales Sánchez: Predoctoral researcher; BSc. in Biology, Universidad de Extremadura (Spain).

 

Cristina Juárez Alia: BSc. in Biochemistry, Universidad de Castilla-La Mancha (Spain).

 

Luis Almodóvar: MD, medical specialist in cardiovascular surgery. BSc in Medicine and Surgery, Universidad Autónoma de Madrid (Spain).

 

Álvaro González Cantero: MD, Universidad de Castilla-La Mancha (Spain).

 

 

 

 

Research lines

 

Degenerative Aortic Stenosis
Degenerative aortic stenosis (DAS) is a chronic and highly prevalent disease that evolves from a thickening of the aortic valves towards severe stenosis and calcification. It represents an elevated economic and social burden given the long asymptomatic periods that make early diagnosis and treatment difficult, and given the fact that there is still no adequate treatment other than surgery.

We have been studying this disease in the laboratory for several years, applying a variety of techniques to different types of samples, including patient’s plasma and tissue,as well as taking advantage of distinct in vitro and in vivo models. The objective of these studies is to improve our understanding of the disease at the molecular level so as to be able to develop new early diagnostic methods, as well as new therapies that act at the asymptomatic stage of the disease.

We are currently developing different projects related to CV risk factors and their relationship with DAS, focusing mainly on atherosclerosis and diabetes mellitus.
   

      - Atherosclerosis
Atherosclerosis is a disease in which lipid deposits accumulate at the walls of arteries (atheroma plaques). This disease can affect any artery in the body, including those of the heart, brain, arms, legs, pelvis and kidneys. We focus our studies on coronary atherosclerosis, which ultimately leads to heart attacks and that may affect the arteries in the brain, provoking strokes. Furthermore, we study the relationship between this pathology and degenerative aortic stenosis given that they share common mechanisms in their development.

 

    - Diabetes mellitus
Both diabetes and DAS occur routinely in the elderly population. Currently, there is evidence that the prevalence of diabetes increases substantially in patients with DAS and that patients with diabetes have higher rates of progression from mild to severe DAS. However, the effects of this disease on the aortic valve are not properly known. Therefore, we have a project focused on the study of the molecular mechanisms that are involved in the development of DAS in patients with diabetes, seeking to identify new predictive and therapeutic targets in these patients.

 

 

Psoriasis and cardiovascular diseases
Patients with psoriasis have a decrease in life expectancy due to cardiovascular disease presenting an increased risk of myocardial infarction at earlier ages than the general population. Since traditional cardiovascular risk factors do not accurately assess the risk of cardiovascular disease in patients with psoriasis, it has been proposed that such individuals should follow a screening for the detection of subclinical atherosclerosis. In recent years, numerous publications have been published emphasizing the need to find a biomarker capable of assessing the adequate cardiovascular risk of these patients in order to minimize their risk through prevention and treatment. From the point of view of clinical applicability, the use of an -omic approach to identify a biomarker of atherosclerosis in psoriasis patients is allocated to revolutionize the current definition of the disease. The development of a new concept that encompasses the set of physiological and pathological changes derived from the pathology, establishing protein profiles/panels, will allow a more precise diagnosis.

 

 

Alzheimer's disease and cardiovascular health
Alzheimer's disease is one of the most important problems in today's society, with a high social and economic burden. Therefore, preventing and/or delaying cognitive decline is a public health priority. The brain changes in Alzheimer's disease can begin 20 years before the symptoms appear, so the development of preventive measures in early stages to delay cognitive decline is essential, especially considering that today Alzheimer's disease has no cure or effective treatment.
A clear relationship has been observed between CV health and the development of Alzheimer's disease, with a clear link between heart and brain. However, the mechanisms involved in this relationship are not completely understood. For this reason, we collaborate with Dr. Felipe Madruga to decipher the molecular and clinical aspects for the prevention and treatment of Alzheimer's disease in patients with cardiovascular disease. We are trying to define the mechanisms related to these pathologies, as well as to identify new therapeutic targets, which may be useful to delay the development of cognitive decline, improving the prognosis and progression of those people who present both pathologies.

 

 

Progeria
Hutchinson-Gilford progeria syndrome, also known as progeria, is an ultrarare genetic disorder characterized by severe premature aging and for which there is no cure. Starting at 1-2 years of age, patients with Progeria begin to show symptoms reminiscent of aging such as alopecia, pigmentation and wrinkling, subcutaneous fat loss and lipodystrophy, muscle atrophy, tooth and bone alterations, and joint stiffness. Furthermore, although they normally lack most traditional cardiovascular risk factors, patients develop cardiovascular diseases and die from complications of atherosclerosis such as myocardial infarction, heart failure or stroke at a mean age of 14.5 years. Currently there is a lack of clinically meaningful shorter-term biomarkers that permit monitoring of disease progression after diagnosis, as well as evaluating patient responses to treatment.
In this project (ProgerOmics) we work with 4 internationally renowned groups to implement a biomarker discovery strategy based on multiomics studies (radiomics, transcriptomics, epigenomics, proteomics and metabolomics) in a mouse model with early and intermediate signs of disease. In addition, these candidate biomarkers will subsequently be evaluated in human samples with the goal of transitioning from basic to clinical research.

 

 

Human Proteome Project
The Human Proteome Project (HPP) aims to identify and quantify the proteins encoded by the more than 20,000 genes that make up the human genome, both in normal and pathological tissue. This has a dual focus, from the basic or fundamental point of view, it aims to describe the entire proteome, generating a deeper knowledge of the biology of human beings, while in more applied terms the aim is to enhance our understanding of prevalent complex diseases. The project intends not only to identify all human proteins but also, their variants (isoforms, post-translational modifications), as well as defining their concentrations in the approximately 230 cell types that make up our bodies. Spain has a corporative participation in this project, with 14 public funded laboratories participating from all over the country, each established at research centres, Universities, Hospitals (Accredited Health Service Research Institutes), and with the ultimate responsibility for the project lying with the National Proteomics Institute (ProteoRed). Furthermore, the proposal was unconditionally approved by the Spanish Proteomics Society (SeProt), many members of which are active in the participating laboratories.

 

 

Projects related to Spinal Lesions and neurological diseases
Our experience in proteomics and metabolomics, and the situation of the laboratory within the Hospital Nacional de Parapléjicos in Toledo facilitates our participation in different studies related to spinal cord lesions, collaborating with the clinicians at the hospital. These include studies into the:

1) Effects of COVID-19 in patients with spinal cord injury (in collaboration eith Dr. Gil Agudo)

2) Efficacy and safety of Growth Hormone (GH) in subjects with spinal cord lesions: a random triple blind clinical trial (in collaboration with Dr. Oliviero)

3) Alternative therapies in pressure ulcers produced in patients with spinal cord lesions due to severe traumatism (in collaboration with Dr. Arévalo).

 

 

 

 

Projects of the last year

 

- IDENTIFICATION OF BIOMARKERS TO MONITOR THE PROGRESSION OF HUTCHINSON-GILFORD PROGERIA SYNDROME (ProgerOmics). Instituto de Salud Carlos III (European Joint Programme on Rare Diseases). 2023-2025.

 

 

- DIABETES MELLITUS IN AORTIC STENOSIS PATIENTS: A RISKY MIX. Junta de Comunidades de Castilla La Mancha. 2022-2024.

 

 

- CHARACTERIZATION OF ATHEROSCLEROSIS IN PSORIASIS USING NOVEL BLOOD PROTEOMIC SIGNATURES (AtheroRiskPso Project). National Psoriasis Foundation Early Career Research Grant (NIH). 2022.

 

- DIABETES MELLITUS IN AORTIC STENOSIS PATIENTS AND ITS IMPLICATIONS FOR ATHEROSCLEROSIS: A RISKY MIX (SUNRISE PROJECT). Instituto de Salud Carlos III. PI21-00384. 2022-2024.

 

 

- DECIPHERING THE BRAIN-CARDIOVASCULAR SYSTEM CONNECTION - THE BRAIN-HEART CONTINUUM. Sociedad Española de Cardiología. 2021-2022 .

 

 

- EFFECTS OF CORONARY ARTERY DISEASE IN THE DEVELOPMENT OF DEGENERATIVE AORTIC STENOSIS: STUDY OF THE DIFFERENTIAL EXPRESSION OF PROTEINS AND THEIR OXIDATIONS. Junta de Comunidades de Castilla - La Mancha. SBPLY/19/180501/00226. 2020-2022.

 

 

- A PROTEOMIC-BASED STUDY TO DISCOVER POTENTIAL MARKERS FOR ATHEROSCLEROSIS IN PSORIASIS PATIENTS. CELGENE, EUROPEAN competitive project. 2020-2022.

 

 

- EARLY DETECTION AND PROGRESSION OF SUBCLINICAL ATHEROSCLEROSIS IN PSORIASIS. LeoPharma, Competitive European project. 2020-2022.

 

 

- MOLECULAR PROFILE OF DEGENERATIVE AORTIC STENOSIS TO PREDICT DISEASE AND DEVELOP NEW THERAPIES: STUDIES ON THE DEGENERATIVE PROCESS. Instituto de Salud Carlos III. PI21-00384. PI18/00995. 2018-2021.