Heart failure

 

Heart failure is one of the leading causes of mortality and hospitalization in Western countries in general and in Spain in particular. Our research lines are focused on characterizing the major structural alterations of the myocardium underlying its functional impairment, which are involved in the development and progression of heart failure.  

Our projects analyze the mechanisms responsible for these alterations in different cardiomyopathies, as well as their impact on cardiac function, in order to understand the pathophysiological basis of heart failure and to identify the key molecules involved. In this context, the group is exploring new therapeutic strategies aimed at correcting the structural alterations in the myocardium of patients with heart failure. The effects of different drugs used in the treatment of heart failure on the myocardium are also being assessed.

In addition, we also have a strong interest in the development of non invasive circulating biomarkers, allowing the evaluation of structural myocardial alterations in a simple, reproducible, sensitive and specific manner. These biomarkers are evaluated in patients in different stages of cardiac diseases. The purpose is to allow the early diagnosis of these alterations, the implementation of a personalized therapy and the monitoring of the effects of treatment.

In order to carry out these projects, we have a multidisciplinary team and a translational research program including the analysis of samples from heart failure patients as well as different experimental models (from cultured cardiac cells to animal models including transgenic mice, rats with genetic hypertension and models of induced heart failure). Our studies go from the characterization of the alterations present at molecular, cellular and tissue level to the assessment of their functional impact through imaging techniques. In addition, we have the necessary tools to identify new therapeutic targets and to develop potential inhibitors. We also have a solid background in validating circulating biomarkers of myocardial remodelling.  

Our main areas of research are the following:

  1. Study of the role of the alterations in the cardiac extracellular matrix in the development of heart failure of different etiologies  (mainly evolving with preserved ejection fraction).

  2. Development of a panel of circulating markers reflecting the different components of myocardial remodeling (i.e. both the extracellular matrix and cardiomyocytes) in patients with heart failure in different stages of the disease.

  3. Evaluation of the impact of co-morbidities such as chronic kidney disease or metabolic alterations (e.g. diabetes mellitus, metabolic syndrome, obesity) on the development of myocardial remodeling and heart failure.

  4. Studies with specific molecules directed against new molecular targets in order to develop new pharmacological interventions that prevent or reverse myocardial damage in heart failure.

Fecha de actualización: Noviembre 2018

Active projects

  • Proyectos de I+D en Salud. AES 2015. Beneficiario: IdiSNA-FIMA

    Título: “Interacción metaloproteinasas-hemostasia, un nuevo mecanismo en la patología cerebrovascular: estrategias terapéuticas basadas en la modulación de la MMP-10”.
    Referencia: PI15/01909.
    I. P.: Aranzazu González Miqueo.
    Duración: 3 años.
    F. Inicio: 01/01/2016      F. Fin: 31/12/2018
    Subvención: 134.915,00 €.
    Financiado: Por el Instituto de Salud Carlos III y cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa”.

    Resumen:
    La insuficiencia cardiaca crónica (IC) constituye una de las principales causas de morbimortalidad, con una alta prevalencia (asociada al envejecimiento), muy mal pronóstico, y siendo causa frecuente de hospitalización. Por lo tanto, existe una necesidad médica no resuelta en el diagnóstico precoz y preciso y en el tratamiento personalizado de estos pacientes. Se sabe que la fibrosis miocárdica contribuye al desarrollo de esta patología y planteamos que las moléculas del eje implicado en el procesamiento y formación del colágeno: la proteinasa carboxi-terminal del procolágeno (PCP), su potenciador (PCPE-1) y la lisil oxidasa (LOX), desempeñan un papel relevante en este proceso, y por lo tanto podrían constituir nuevas dianas terapéuticas y/o biomarcadores. Para validar esta hipótesis planteamos: 1) Establecer el papel del eje PCP/PCPE-1-LOX en el desarrollo de fibrosis miocárdica en la IC en condiciones asociadas con el envejecimiento como la hipertensión arterial, la estenosis aórtica, la fibrilación auricular y el envejecimiento en pacientes y en modelos animales (rata espontáneamente hipertensa, modelo de constricción aórtica, ratón SAMP8 de envejecimiento acelerado, y ratón transgénico con sobre-expresión condicional cardíaca del PCPE-1). 2) Evaluar el efecto del bloqueo del eje PCP/PCPE-1-LOX sobre el desarrollo de fibrosis y el deterioro cardiaco en modelos animales. 3) Analizar en los pacientes disponibles la utilidad diagnóstica (asociación con parámetros de morfología y función) y pronóstica (eventos cardiovasculares, descompensación y/o incidencia de IC y muerte) de los niveles séricos del PICP como marcador de la actividad del sistema PCP/PCPE-1 y de CITP como marcador del grado de entrecruzamiento.



"Studies with specific molecules directed against new molecular targets in order to develop new pharmacological interventions that prevent or reverse myocardial damage in heart failure.", Arantxa González, investigadora principal.

Contact

Contact:
Nerea Cano
Avda. Pío XII, 55
31008 Pamplona
España

(+34) 948 194 700 Ext. 3044
ncano@unav.es