Molecular characterization of vascular pathogenesis

Research summary:

We are interested in uncovering novel mediators of cardiovascular pathogenesis, one of the major causes of death worldwide, because these mediators might become novel targets for therapeutic intervention. To this end, we use a combination of in vitro and in vivo experimental approaches involving transcriptomics, proteomics, cellular and molecular analysis, mouse models, and advanced imaging techniques.

Our pioneering studies, in collaboration with the group of Dr. J.M. Redondo (CNIC), show that deficiency of the metalloproteinase Adamts1 leads to thoracic aorta aneurysm (TAA) in mice due to increased Nos2-dependent NO production. We also showed that TAA was reversed using pharmacological NOS2 inhibition in mouse models, raising the possibility that blocking NO signaling could be a novel treatment for TAA. Indeed, we are pursuing clinical trials with NOS2 inhibitors in Marfan syndrome, a heritable life-threatening disease in which TAA accounts for over 90% of its mortality. These findings changed our view of the pathophysiology of TAA and prompted us to further explore the molecular and biomechanical mechanisms of TAA in collaboration with other international research groups. Much of our recent effort focuses on the identification of additional mediators of these diseases.

We also search for genes mediating pathological vascular wall remodeling, a key process in the development of hypertension and arterial diseases such as atherosclerosis and aneurysm. We had determined that calcineurin and its downstream effector Rcan1 are essential mediators of atherosclerosis, restenosis, and abdominal aorta aneurysm (AAA). Our studies allowed the identification of new pathophysiological mechanisms and new therapeutic targets in aortic diseases. Using tissue-specific inducible knockout mice, we have also uncovered a homeostatic role for Rcan1 in the aorta and that its genetic inactivation in the adult mouse predisposes to hypertension-induced intramural hematoma and subsequent AAA through mechanisms involving GSK-3b, ROCK and smooth muscle Myosin. These results prompted us to follow new exciting avenues of research into the pathogenesis of aortic diseases. In particular, we have initiated a comprehensive study aimed at identifying the role of calcineurin in the aortic transcriptome, proteome, and phosphoproteome regulated by hypertensive stimuli such as angiotensin II. We believe that these studies will identify therapeutic targets for AAA and novel therapeutic targets for arterial hypertension.

Image

Figure 1. Transcriptomics, proteomics, tissue staining analysis, and primary cell cultures of mouse models of disease and/or patient-derived samples are used to dissect the major signaling pathways that cause arterial diseases, such as aortic aneurysm and arterial hypertension, and identify novel targets for therapeutic intervention. Genetic manipulation and in vivo lentiviral-mediated transduction are then used to generate new mouse models for validation of these targets. The efficacy of novel treatments is assessed longitudinally in vivo by ultrasound imaging of the heart and vessels and ex vivo by tissue analysis.

Image

* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Campanero GarcíaMiguel R.2274554mcampanero(at)cbm.csic.esE. Investigadores Científicos de Organismos Públicos
Hernández AlcántaraAlberto2274587ahernandez(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Herranz MartinEstela 2274587eherranz(at)cbm.csic.esGJ-AI y TL_Titulado Sup. Actividades Técn. y Prof.GP1
Martínez NuñezPatricia2274587pmartinez(at)cbm.csic.esTécnico Sup. Actividades Tec. y Profes.GP3
Sun Yilin4587Contrato Predoctoral

Relevant publications:

  • A. de la Fuente-Alonso, M. Toral, A. Alfayate, M.J. Ruiz-Rodríguez, E. Bonzón-Kulichenko, G. Teixido-Tura, M.J. Méndez-Olivares, D. López-Maderuelo, I. González-Valdés, E. García-Izquierdo, S. Mingo, C.E. Martín, L. Muiño-Mosquera, J. De Backer, J.F. Nistal, A. Forteza, A. Evangelista, J. Vázquez, *M.R. Campanero, and *JM Redondo. *Co-senior & corresponding authors. Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO. Nat. Commun. (under second revision) (2020).
  • C. Martín-Cortázar, Y. Chiodo, R. Jiménez-P., M. Bernbé, M.L. Cayuela, T. Iglesias, and M.R. Campanero. CDCA7 finely tunes cytoskeleton dynamics to promote lymphoma migration and invasion. Haematologica. 105(3): 730-740 (2020). IF2019: 7,12 (7/76 in Hematology).
  • S Villahoz, PS Yunes-Leites, N Méndez-Barbero, K Urso, E.Bonzon-Kulichenko, S Ortega, J Vazquez, S Offermanns, *JM Redondo, and *MR Campanero. *Co-senior & corresponding authors. Conditional deletion of Rcan1 predisposes to hypertension-mediated aortic intramural hematoma and subsequent aneurysm and lethal dissection. Nat Commun 9(1): 4795 (2018). IF2018: 11,88 (5/69 in Multidisciplinary Sciences).
  • R. Jiménez-P., C. Martín-Cortázar, O. Kourani, Y. Chiodo, R. Cordoba, M.P. Domínguez-Franjo, J.M. Redondo, T. Iglesias, and M.R. Campanero. CDCA7 is a critical mediator of lymphomagenesis that selectively regulates anchorage-independent growth. Haematologica. 103(10): 1669-1678 (2018). IF2018: 7,57 (7/73 in Hematology).
  • J. Oller, N. Méndez-Barbero, E.J. Ruiz, S. Villahoz, M. Renard, L.I. Canelas, A.M. Briones, R. Alberca, N. Lozano-Vidal, M.A. Hurlé, D. Milewicz, A. Evangelista, M. Salaices, J.F. Nistal, L.J. Jiménez-Borreguero, J. DeBacker, *M.R. Campanero, and *J.M. Redondo. *Co-senior & corresponding authors. Nitric oxide mediates aortic disease in mice deficient in the metalloprotease Adamts1 and in a mouse model of Marfan syndrome. Nat. Med. 23(2): 200-212 (2017). IF 2017: 32,62 (1/124 in Medicine, Research & Experimental). Destacado por Science: http://science.sciencemag.org/content/355/6324/twil; Destacado por Biocentury: Inducible nitric oxide synthase 2 (NOS2; iNOS).
  • J. Alvaro-Blanco, Y. Chiodo, K. Urso, C. Martín-Cortázar, O. Kourani, M. Rodriguez-Martinez, E. Calonge, J. Alcamí, J.M. Redondo, T. Iglesias, and M.R. Campanero. MAZ induces MYB expression during the exit from quiescence via de E2F site in the MYB promoter. Nucleic Acids Res. 45(17): 9960-9975 (2017). IF2017: 11,56 (14/286 in Biochemistry & Molecular Biology).
  • J. Oller, A. Alfranca, N. Méndez-Barbero, S. Villahoz, N. Lozano-Vidal, M. Martín-Alonso, A.G. Arroyo, A. Escolano, A.L. Armesilla, *M.R. Campanero*, and *J.M. Redondo. *Co-senior & corresponding authors. C/EBPß and NFAT differentially regulate Adamts1 induction by stimuli associated with vascular remodeling. Mol. Cell Biol. 35(19): 3409-3422 (2015). IF 2015: 4,43 (66/289 in Biochemistry & Molecular Biology)
  • N. Méndez-Barbero, V. Esteban, S. Villahoz, A. Escolano, K. Urso, A. Alfranca, C. Rodríguez, S.A. Sánchez, T. Osawa, V. Andrés, J. Martínez-González, T. Minami, *J.M. Redondo, and *M.R. Campanero *Co-senior & corresponding authors. A major role for RCAN1 in atherosclerosis progression. EMBO Mol. Med. 5:1901-1917 (2013). IF 2013: 8,25 (8/122 in Medicine, Research & Experimental)
  • Molina-Privado, R. Jiménez-P., S. Montes-Moreno, Y. Chiodo, M. Rodríguez-Martínez, L. Sánchez-Verde, T. Iglesias, M.A. Piris, and M.R. Campanero. E2F4 plays a key role in Burkitt lymphoma tumorigenesis. Leukemia. 26(10): 2277-2285. (2012). IF 2012: 10,16 (2/67 in Hematology; 8/196 in Oncology)
  • V Esteban, N Méndez-Barbero, LJ Jiménez-Borreguero, M Roqué, L Novensá, AB García-Redondo, M Salaices, L Vila, ML. Arbonés, *M.R. Campanero, and *JM Redondo. *Co-senior & corresponding authors. Regulator of calcineurin 1 mediates pathological vascular wall remodeling. J. Exp. Med. 208: 2125-2139. (2011). IF 2011: 13,85 (2/110 in Medicine, Research & Experimental). Seleccionado por Faculty of 1000 (Muller W: 2012. F1000.com/13418975)

Doctoral theses:

  • Irene Molina Privado (2009). Estudio de las bases moleculares de la formación del Linfoma de Burkitt para la identificación de posibles marcadores diagnósticos y dianas terapéuticas. Universidad Autónoma de Madrid. Director: Miguel R. Campanero
  • Lorena Martínez Gac (2009). Estudio de los mecanismos implicados en la regulación transcripcional de los genes CCNG2 Y C-MYC. Universidad Autónoma de Madrid. Directores: Miguel R. Campanero y Ana Clara Carrera.
  • Raúl Jiménez Pérez (2013). Identificación y caracterización funcional de genes implicados en la transformación maligna del compartimento linfocitario. Universidad Autónoma de Madrid. Director: Miguel R. Campanero.
  • Nerea Méndez Barbero (2014). Estudio del papel de calcineurina y Rcan1 en el remodelado patológico de la pared vascular. Universidad Autónoma de Madrid. Directores: Miguel R. Campanero y Juan Miguel Redondo.
  • Yuri Chiodo (2017). Cell death, cell growth and cell cycle regulation by the Retinoblastoma family. Universidad Autónoma de Madrid. Directores: Miguel R. Campanero y Juan Miguel Redondo.
  • Jorge Oller Pedrosa (2017). Identification of the metalloproteinase Adamts1 and Nitric Oxide as new therapeutic targets in aortic diseases. Universidad Autónoma de Madrid. Directores: Miguel R. Campanero y Juan Miguel Redondo.
  • Silvia Villahoz Lázaro (2018). Effects of conditional deficiency of Rcan1 in pathological vascular wall remodeling (Tesis Europea). Universidad Autónoma de Madrid. Directores: Miguel R. Campanero y Juan Miguel Redondo.
  • Carla Martín Cortázar (2019). Invasión, migración y dinámica del citoesqueleto de células de linfoma mediadas por CDCA7. Universidad Autónoma de Madrid. Director: Miguel R. Campanero.
  • Omar Kourani Méndez (2019). Papel del sistema del glutatión en la adaptación y resistencia de los tumores linfoides al estrés oxidativo. Universidad Autónoma de Madrid. Director: Miguel R. Campanero.

Licensed patents:

  • Procedimiento de identificación de pacientes con linfoma de Burkitt esporádico, procedimiento de identificación y uso de compuestos para el tratamiento de linfoma de Burkitt esporádico. I. Molina-Privado y Miguel R. Campanero. PCT/ES2008/070182. País de prioridad: Internacional salvo USA. Fecha: octubre de 2007.  Entidad titular: CSIC/UAM; Licenciada a BIOTOOLS Biotechnological & Medical Laboratories S.A. el 29 de abril de 2008.
  • In vitro method for identifying thoracic aortic aneurysms (TAA) in a subject. J.M. Redondo, J. Oller, N. Méndez-Barbero y Miguel R. Campanero. PCT/EP2016/082925. País de prioridad: Internacional excepto USA. Fecha de prioridad: marzo de 2016; Entidad titular: CNIC/CSIC/UAM. Licenciada a SPHERIUM BIOMED S.L. el 21 de septiembre de 2018. Patente USA (Nº 16/083,165) concedida el 16 de septiembre de 2020.

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand

COOKIES POLICY

What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

    Depending on the purpose for which the data obtained through cookies are processed, we can distinguish between:

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

  • Accept cookies: if the user presses the acceptance button, this warning will not be displayed again when accessing any page of the portal.
  • Review the cookies policy: the user can access to this page in which the use of cookies is detailed, as well as links to modify the browser settings.

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: