Extracellular matrix remodeling in the cardiovascular system

Research summary:

Proper synthesis and assembly of extracellular matrix components is essential to provide cells and tissues with their biological and biomechanical properties, a circumstance particularly relevant in the cardiovascular system. Lysyl oxidases (LOX) catalyze the initiation step in the formation of covalent cross-links in fibrillary collagens and elastin, and thereby they constitute a family of enzymes essential for the stabilization and maturation of the extracellular matrix. In our group, we investigate the molecular mechanisms regulating the expression and activity of LOX enzymes, as well as their pathophysiological relevance in the development of cardiovascular diseases.

Within this context, in the last years the group has explored various research lines including the role of LOX in the development of cardiovascular diseases, particularly in the formation of aneurysms in Marfan syndrome and in the heart response to myocardial infarction, where the expression of these enzymes has been shown to have an opposing role in disease progression. In addition, we have been interested in the potential biotechnological applications of the knowledge of the biology of LOX proteins. To this respect, we have implemented protocols to enhance the efficiency of the deposition of collagen from cell cultures for their use in the generation of matrices suitable for tissue repair in bioengineering. Additionally, we investigate the evolutive history of the members of the LOX family, with particular emphasis in their capacity to crosslink collagen and elastin, as an approach to infer their biochemical and structural features. Very recently, we have opened a new line of research dealing with the regulation of LOX enzymatic activity by proteolysis, where our current study intends to identify proteases processing LOX isoforms as well as to analyze the contribution of these proteolytic events to their biological role.

 

 

Image

Lysyl oxidase (LOX) inhibition induces ascending aortic dilatation in Marfan mice. (A) Ascending aortic diameter as measured by echocardiography prior to the beginning of the treatment (baseline), and 4 and 8 weeks after the administration of the LOX inhibitor, b-aminopropionitrile (BAPN), or placebo in Marfan mice. Values are means + SEM. *P<0.05. (B) Gross morphology of representative aortas of mice treated with placebo or BAPN during 8 weeks.

Image


* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Rodríguez PascualFernando1034505frodriguez(at)cbm.csic.esE.Científicos Titulares de Organismos Públicos de Investigación
Rosell GarcíaTamara1034456trosell(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1 66%

Relevant publications:

  • Rodríguez-Pascual, F. How evolution made the matrix punch at the multicellularity party (2019) Journal of Biological Chemistry, 294 (3), pp. 770-771.
  • Rosell-García, T., Palomo-Álvarez, O., Rodríguez-Pascual, F. A hierarchical network of hypoxia-inducible factor and SMAD proteins governs procollagen lysyl hydroxylase 2 induction by hypoxia and transforming growth factor β1 (2019) Journal of Biological Chemistry, 294 (39), pp. 14308-14318.
  • Rosell-García, T., Paradela, A., Bravo, G., Dupont, L., Bekhouche, M., Colige, A., Rodriguez-Pascual, F. Differential cleavage of lysyl oxidase by the metalloproteinases BMP1 and ADAMTS2/14 regulates collagen binding through a tyrosine sulfate domain (2019) Journal of Biological Chemistry, 294 (29), pp. 11087-11100.
  • Rosell-Garcia, T., Rodriguez-Pascual, F. Enhancement of collagen deposition and cross-linking by coupling lysyl oxidase with bone morphogenetic protein-1 and its application in tissue engineering (2018) Scientific Reports, 8 (1), art. no. 10780, .
  • Rodriguez-Pascual, F., Rosell-Garcia, T. Lysyl Oxidases: Functions and Disorders (2018) Journal of Glaucoma, 27, pp. S15-S19.
  • Rodriguez-Pascual, F., Slatter, D.A. Collagen cross-linking: Insights on the evolution of metazoan extracellular matrix (2016) Scientific Reports, 6, art. no. 37374, .
  • González-Santamaría, J., Villalba, M., Busnadiego, O., López-Olañeta, M.M., Sandoval, P., Snabel, J., López-Cabrera, M., Erler, J.T., Hanemaaijer, R., Lara-Pezzi, E., Rodríguez-Pascual, F. Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction (2016) Cardiovascular Research, 109 (1), pp. 67-78.
  • Busnadiego, O., Gorbenko del Blanco, D., González-Santamaría, J., Habashi, J.P., Calderon, J.F., Sandoval, P., Bedja, D., Guinea-Viniegra, J., Lopez-Cabrera, M., Rosell-Garcia, T., Snabel, J.M., Hanemaaijer, R., Forteza, A., Dietz, H.C., Egea, G., Rodriguez-Pascual, F. Elevated expression levels of lysyl oxidases protect against aortic aneurysm progression in Marfan syndrome (2015) Journal of Molecular and Cellular Cardiology, 85, pp. 48-57.
  • Grau-Bové, X., Ruiz-Trillo, I., Rodriguez-Pascual, F. Origin and evolution of lysyl oxidases (2015) Scientific Reports, 5, art. no. 10568, .
  • Busnadiego, O., González-Santamaría, J., Lagares, D., Guinea-Viniegra, J., Pichol-Thievend, C., Muller, L., Rodríguez-Pascual, F. LOXL4 is induced by transforming growth factor β1 through Smad and JunB/Fra2 and contributes to vascular matrix remodeling (2013) Molecular and Cellular Biology, 33 (12), pp. 2388-2401.

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: