Vascular Pathophysiology

Grupo de Fisiopatología Vascular

Vascular Pathophysiology

 

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

 

Vascular Pathophysiology Group has developed a series of techniques for proteomics and metabolomics analysis that can be used in the identification of prognostic, diagnostic and/or therapeutic biomarkers of cardiovascular and neurological disorders, as well as spinal cord injury-related diseases.

 

Together with Dr. Vivanco (IIS-Foundation Jiménez Díaz) we were the pioneers in the cultivation and analysis of arteries with plaques and aortic valve stenosis, where we used their secretome for the first time and identified a number of new biomarkers. Given a likely connection between the development of atherosclerosis and aortic stenosis, we are presently collaborating with the group of Dr. Vivanco to find common mechanisms in both diseases.

 

As a result of all these activities, Drs. Barderas and Padial have written various scientific articles, reviews and book chapters on clinical proteomics applied to vascular diseases, as well as on the development and use of metabolomics to search for biomarkers in these pathologies.

 

Taking advantage of a perfect work environment at the National Hospital for Paraplegics, where every day is about improving the quality and expectancy of patients´ life, we have established colaborations with clinical groups working in spinal cord injury, pressure ulcers and stroke with the objective of applying our knowledge to the study of these conditions and continuing with the development of translational research. 

 

Furthermore, the group is a part of the Human Proteome Project within the Madrid-Toledo node.

 

 

 

Selected publications

 

- Roselló-Lletí E, Tarazón E, Barderas MG, Ortega A, Molina-Navarro MM, Martínez A, Lago F, Martínez-Dolz L, González-Juanatey JR, Salvador A, Portolés M, Rivera M. ATP synthase subunit alpha and LV mass in ischaemic human hearts.J Cell Mol Med. 2015;19(2):442-51. doi: 10.1111/jcmm.12477.

 

- Roselló-Lletí E, Tarazón E, Barderas MG, Ortega A, Otero M, Molina-Navarro MM, Lago F, González-Juanatey JR, Salvador A, Portolés M, Rivera M. Heart mitochondrial proteome study elucidates changes in cardiac energy metabolism and antioxidant PRDX3 in human dilated cardiomyopathy. PLoS One. 2014; 9(11):e112971. doi: 10.1371/journal.pone.0112971. 

 

- 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; 23; 109:368-81. doi: 10.1016/j.jprot.2014.07.016. 

 

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

 

- Posada-Ayala M, Zubiri I, Martin-Lorenzo M, Sanz-Maroto A, Molero D, Gonzalez-Calero L, Fernandez-Fernandez B, de la Cuesta F, Laborde CM, Barderas MG, Ortiz A, Vivanco F, Alvarez-Llamas G. Identification of a urine metabolomic signature in patients with advanced-stage chronic kidney disease. Kidney Int. 2014; 85(1):103-11. doi: 10.1038/ki.2013.328.

 

 

 

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 Patent registration No: PCT/ES2011/070365 (2011).

 

 

 

Personnel

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

 

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

 

Fernando de la Cuesta Marina: Postdoctoral researcher; PhD. in Biology, Universidad de Complutense, Madrid (Spain).

 

Rafael Moreno Luna: Postdoctoral researcher;  PhD. in Biology, Universidad de Córdoba (Spain).

 

Laura Mouriño Álvarez: Postdoctoral researcher; PhD. in Biology, Universidad de Alcalá de Henares, Madrid (Spain).

 

Montserrat Baldán Martín: Predoctoral researcher; BSc. in Biology, Universidad Autonoma, Madrid (Spain).

 

Finn Olof Akerström: Predoctoral researcher; MD. Faculty of Medicine, Leicester (UK).

 

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

 

 

 

 

Ongoing projects
     

 

- HPP CARDIOVASCULAR INITIATIVE: AGE RELATED VARIATIONS IN THE MOLECULAR AND OMIC PROFILE  AND CARDIOVASCULAR RISK STRATIFICATION

PI: Maria G. Barderas. Funded by  FIS (2014-2017)

 

- BIOMOLECULAR  AND BIOINFORMATICS RESOURCES PLATFORM THAT LEADS PROTEORED

PI: Maria G. Barderas. Funded by FIS (Support projects  destined to science and health technologies; Call 2013-PT13 / 0001/0013; 2013-2017 renewed annually).

 

- COMPREHENSIVE APPROACH TO RESISTANT HYPERTENSION: IMPROVING DIAGNOSIS AND TREATMENT AND SEARCHING FOR BIOLOGICAL MARKERS OF THERAPEUTIC RESPONSE

PI: Fernando de la Cuesta Marina. Funded by the Health Research Fund (PI13 / 01581, Notice 2013; 2013-2016).

 

- THEMATIC NETWORKS FOR COOPERATIVE RESEARCH: CARDIOVASCULAR RESEARCH NETWORK

PIs: R. Luis Padial and Maria G. Barderas. Funded by the Health Research Fund (ISCIII; Reference: RD12 / 0042/0071; 2012-2015). 

 

- NEW PROTEOMICS AND METABOLOMICS APPROACHES IN THE STUDY OF TARGET ORGANS DEVELOPMENT IN HYPERTENSIVE PATIENTS TREATED WITH RENIN-ANGIOTENSIN SYSTEM BLOCKERS

PI: Maria G. Barderas; Funded by the Health Research Fund (ISCIII;   Reference: PI-1102239; 2012-2014).

 

 

 

Research lines
     

- DEGENERATIVE AORTIC STENOSIS: A STUDY OF PATHOGENIC ASPECTS BY USING PROTEOMICS ANALYSIS

Aortic stenosis (AS) is a degenerative disease highly prevalent in developed countries and it is also a cause for the largest number of aortic valve replacements. Both the aging population and the age induced increase in degenerative AS predict a significant increase in its incidence in the coming years.

The main objective of this study is to employ proteomics and metabolomics techniques in the analysis of aortic valves affected by degenerative AS in order to achieve a better understanding of its pathogenesis prior to the development of effective preventive therapies.

 

- NEW PROTEOMICS AND METABOLOMICS APPROACHES IN THE STUDY OF THE EVOLUTION OF ORGANS: TARGETS IN HIPRETENSIVE PATIENTS TREATED WITH RENIN -ANGIOTENSIN SYSTEM BLOCKERS

The development of the cardiorenal organ damage in chronic suppression of the renin-angiotensin-aldosterone system (RAAS) occurres in normal clinical practice and serves to predict the development of cardiorenal events. The objective of this project is to determine the role of proteomics and metabolomics in predicting the damage occurrence and a dual RAAS suppression by means of a direct renin inhibitor or an aldosterone blocker. Therefore, we study the plasma and urine of patients with this profile using a battery of metabolomics and proteomics techniques to identify potentially new protein profiles and metabolite traces. A greater predictability and better RAAS suppression will in turn lead to a better prognosis for cardiorenal patients. 

 

- SEARCH FOR BIOMARKERS: CIRCULATING ENDOTHELIAL CELLS –BASED PROGNOSIS AND DIAGNOSIS IN PATIENTS WITH STROKE AND ACUTE MYOCARDIAL INFARCTION BY MEANS OF PROTEOMICS ANALYSIS

Recent studies have shown that a good endothelial function is essential in many pathophysiological conditions. In fact, it is known that circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) are markers of endothelial function. Furthermore, it has been thought that the EPCs may be involved in endothelial repair/ regeneration processes and that their balance with respect to the CEC may also be important in the evolution of certain pathologies. The objective of this research line is to provide new knowledge on the potential diagnostic value and evolution of these cells and their proteomic characterization, which would allow us to break new ground in preventing and finding new treatments for cerebral infarction and the acute myocardial infarction.

 

- HUMAN PROTEOME PROJECT

The project's main goals are to identify and quantify all proteins encoded by more than 20000 genes that make up the human genome, both in normal and pathological tissues. Thus, its goal is twofold: basic or fundamental- for providing a complete description of the proteome and achieving a detailed knowledge of human biology, and applied - to achieve a better understanding of most frequent complex diseases. The project involves the identification of all human proteins and their variants (isoforms and posttranslational modifications) and the quantification of their concentrations in approximately 230 cell lines that constitute our body. The Spanish participation is of corporate type with the 14 participating laboratories, distributed throughout Spain, the CSIC, various universities, hospitals, accredited health research institutes and research centers. The National Institute of Proteomics (ProteoRed ) is the entity responsible for the project, whose general coordinator Juan Pablo Albar is currently a member of the Executive Committee of the HUPO, the international organization that coordinates all the activities related to this project. The proposal counts with the unconditional support of the Spanish Proteomics Society (SeProt) who’s numerous members also form parts of the participating laboratories.

The knowledge we acquired within the area of ​​proteomics and metabolomics has greatly advanced our understanding of cardiovascular-related spinal cord injuries. That is why we have developed the above projects in collaboration with the National Hospital of Paraplegics.