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 implicated in physiopathological mechanisms of several diseases, mainly cardiovascular (CV) diseases, through –OMICS tools, among others molecular biiology 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.

 

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 5 years

 

Pubmed: MG.Barderas

 

1: 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.PubMed PMID: 29752279; PubMed Central PMCID: PMC6031362.

 

2: Baldan-Martin M, Rodríguez-Sánchez E, González-Calero L, RuilopeLM,Alvarez-Llamas G, Barderas MG, Ruiz-Hurtado G. Translational science in albuminuria: a new view of de novo albuminuria under chronic RAS suppression.ClinSci (Lond). 2018 Apr 6;132(7):739-758. doi: 10.1042/CS20180097. Print 2018Apr 16. Review. PubMed PMID: 29626149.

 

3: Baldan-Martin M, Lopez JA, Corbacho-Alonso N, Martinez PJ, Rodriguez-Sanchez E, Mourino-Alvarez L, Sastre-Oliva T, Martin-Rojas T, Rincón R, Calvo E, Vazquez J, Vivanco F, Padial LR, Alvarez-Llamas G, Ruiz-Hurtado G, Ruilope LM, Barderas MG. Potential role of new molecular plasma signatures on cardiovascular risk stratification in asymptomatic individuals. Sci Rep. 2018 Mar 19;8(1):4802. doi: 10.1038/s41598-018-23037-7. PubMed PMID: 29555916; PubMed Central PMCID:PMC5859270.

 

4: 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. PubMed PMID:27256770; PubMed Central PMCID: PMC4891820.

 

5: 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. Epub 2016 May 23. PubMed PMID: 27217411.

 

6: Martin-Rojas T, Mourino-Alvarez L, Alonso-Orgaz S, Rosello-Lleti E, Calvo E, Lopez-Almodovar LF, Rivera M, Padial LR, Lopez JA, de la Cuesta F, BarderasMG.iTRAQ proteomic analysis of extracellular matrix remodeling in aortic valvedisease. Sci Rep. 2015 Dec 1;5:17290. doi: 10.1038/srep17290. PubMed PMID:26620461; PubMed Central PMCID: PMC4664895.

 

7: Martin-Lorenzo M, Martinez PJ, Baldan-Martin M, Lopez JA, Minguez P, Santiago-Hernandez A, Vazquez J, Segura J, Ruiz-Hurtado G, Vivanco F, Barderas MG, Ruilope LM, Alvarez-Llamas G. Urine Haptoglobin and Haptoglobin-Related Protein Predict Response to Spironolactone in Patients With Resistant Hypertension. Hypertension. 2019 Apr;73(4):794-802. doi:10.1161/HYPERTENSIONAHA.118.12242. PubMed PMID: 30712426.

 

8: Vélez P, Parguiña AF, Ocaranza-Sánchez R, Grigorian-Shamagian L, Rosa I, Alonso-Orgaz S, de la Cuesta F, Guitián E, Moreu J, BarderasMG,González-Juanatey JR, García Á. Identification of a circulating microvesicle protein network involved in ST-elevation myocardial infarction. ThrombHaemost. 2014 Oct;112(4):716-26. doi: 10.1160/TH14-04-0337. Epub 2014 Jul 10. PubMed PMID: 25007837.

 

9: Alonso-Orgaz S, Moreno-Luna R, López JA, Gil-Dones F, Padial LR, Moreu J, de la Cuesta F, Barderas MG. Proteomic characterization of human coronary thrombus in patients with ST-segment elevation acute myocardial infarction. J Proteomics.  2014 Sep 23;109:368-81. doi: 10.1016/j.jprot.2014.07.016. Epub 2014 Jul 24.PubMed PMID: 25065646.

 

10: 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. Epub 2016 Sep 26. PubMed PMID: 27716559.

 

 

 

Patents

 

- PATENT TITLE: METHOD AND KIT FOR DIAGNOSIS AND PROGNOSIS OF CHRONIC KIDNEY DISEASE IN A HUMAN SUBJECT

INVENTORS: Maria Ayala Posada, Maria G. Bard, Gloria Alvarez-Llamas, Fernando Vivanco Martinez. 

SPANISH Patent registration No: P201330663 (2013).

 

 

- PATENT TITLE: PROGNOSTIC METHOD FOR AORTIC STENOSIS UTILIZNG ALPHA 1 ANTICHYMOTRYPSIN AS A MARKER

INVENTORS: Tatiana Martin-Rojas, Felix Gil-Dones, Verónica M. darde, Luis R. Padial, Maria G. Barderas.

SPANISH Patent registration No: P201030759 (2010).

 

- PATENT TITLE: PROGNOSTIC METHOD FOR AORTIC STENOSIS UTILIZNG ALPHA 1 ANTICHYMOTRYPSIN AS A MARKER

INVENTORS: Tatiana Martin-Rojas, Felix Gil-Dones, Verónica M. darde, Luis R. Padial, Maria G. Barderas.

EUROPEAN Patentregistration No: PCT/ES2011/070365 (2011).

 

 

 

Personnel

 

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

 

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

 

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

 

Tatiana Martín Rojas: Postdoctoral researcher; PhD. in Biochemistry, Universidad Complutense, Madrid (Spain)

 

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

 

Tamara Sastre Oliva:Labtechnician; BSc. in Biology, Universidad Alcalá de Henares, Madrid (Spain).

 

Germán Hernández Fernández:Labtechnician; Técnico de laboratorio. Técnico Superior de laboratorio de diagnóstico clínico, IES. Juanelo Turriano, Toledo.

 

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

 

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

 

 

 

 

Research lines

 

Stratification of long- and mid-term vascular risk (“lifetime risk”)

Cardiovascular (CV) diseases are the main cause of death in developed countries. However, thanks to different epidemiological studies, it is now possible to calculate the risk of suffering CV complications in the mid-term (5-10 years). Nevertheless, the large majority ofpatients that have a low risk of suffering CVevents in the short- ormid-term have a higher risk of suffering such events in the long-term if the “lifetime risk” is estimated. This is due to that fact that these risk calculations are only reliable in more elderly patients.

 

In this context, we are carrying out a translational study aimed at defining the molecular profiles that allow us to adequately stratify the CV risk in groups of patients with different ages,in order to be capable of improving preventive strategies by applying them early.

 

 

Arterial Hypertension

Arterial hypertension (AHT) is the principal risk factor associated to CV diseases and thus, it is a key mediator in the progression of CV and Kidney damage. Currently, the use of drugs that inhibit the renin angiotensin aldosterone system (RAAS) are considered to be the best therapy to manage AHT, although CV disease progresses in many patients despite receiving these drugs. Furthermore, there are patients with resistant AHT that do not respond to the treatment with RAAS blockers. These patients are generally subjected to sympathetic adrenal denervation as an alternative to the normal treatments.

 

The goal of this line of research is to analyze the affects and the evolution of the target organs in patients treated with RAASblockers and/orsympathetic adrenal denervation. This will allow biological markers to be identified that are capable of predicting the response to treatment, as well as helping us to understand the mechanisms that are implicatedin the tissue damage which occurs.

 

 

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 understandingof the disease at the molecularlevel so as to be able todevelop newearly diagnostic methods,as well as new therapies that act at the asymptomatic stage of the disease.

 

 

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.

 

 

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

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

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

 

 

 

Ongoing projects

 

- MOLECULAR PROFILES OF HUMAN AORTIC STENOSIS APPLIED TO PREDICT THE DISEASE AND TO DEVELOP NEW THERAPIES: INSIGHTS INTO DEGENERATIVE PROCESS.

IP: Maria G. Barderas. Financiado por FIS (2018-2021). PI18/00995

 

 

- GRANT PRB3

IP: Fernando Corrales. Funded by (2017-2019). PT17/0019/0001

 

 

- IN VITRO STENT ENDOTHELIZATION

IP: Maria G. Barderas. Funded by Abbott.

 

 

- BIOMOLECULAR AND BIOINFORMATIC RESOURCES PLATFORM ADDRESSED TO THE PROTEORED.

IP: Maria G. Barderas. Funded by FIS (2013-PT13/0001/0013; 2013-2017, annually renewed).