Descripción del proyecto
Interacciones neurovasculares en el corazón que envejece
El riesgo de deterioro de la salud cardiovascular aumenta a medida que envejecemos. Varios factores, como los cambios electrofisiológicos, predisponen a los ancianos al riesgo de padecer arritmias, pero aún no se conocen bien los mecanismos detrás de los cambios fisiopatológicos relacionados con la edad. El equipo del proyecto Neuroheart, financiado con fondos europeos, demostrará que el deterioro de la interfaz neurovascular en el corazón que envejece puede ser responsable de las afecciones relacionadas con la edad. Se centrará en los axones del corazón y el papel de la semaforina 3a en las células endoteliales del corazón que envejece, así como en la reducción de la densidad neuronal. En Neuroheart, se examinará la estabilidad eléctrica y las arritmias, el secretoma nervioso y la interacción entre las neuronas y la vasculatura, todo lo cual mejorará la comprensión de las interacciones neurovasculares en el corazón que envejece.
Objetivo
Aging is a major risk factor for impaired cardiovascular health. The aging myocardium is characterized by endothelial cell dysfunction, diastolic and systolic impairment, increased hypertrophy and fibrosis and electrophysiological alterations that predisposes the elderly to arrhythmic risk. The mechanism of age-associated pathophysiological alterations are incompletely understood. In preliminary data, we report that aging is associated with a decline in axon density in the heart. Since vessels align with nerves and this interplay is critical for tissue homeostasis in other organs, we postulate that an impairment of the neuro-vascular interface in the aging heart may contribute to age-associated pathologies.
To address this hypothesis, we will first characterise axon extension and patterning of different nerve fibres in the heart. Second, we will decipher the underlying mechanisms mediating the reduction of axon density in the aging heart. Based on preliminary data documenting an induction of the repulsive Semaphorin 3a (SEMA3A) in endothelial cells of the aging heart, we will address if endothelial SEMA3a mediates the effect. Third, we will determine the consequences of reduced neuron density: We will i) study electrical stability and arrhythmias; ii) We will explore the nerve secretome aiming to identify paracrine signals that possibly control cardiac tissue homeostasis and age-associated alterations. iii) We will assess the cross-talk of neurons with age-associated cardiac inflammation. Finally, we will determine whether senescence may contribute to neuro-vascular alterations during aging. We will extend preliminary data suggesting that senolytics interfere with the age-induced decline in axon density.
Together, these data will decipher the so far unexplored role of the neuro-vascular interaction in the aging heart. We believe that restoring or preserving a functional cross-talk between neurons and the vasculature may contribute to healthy cardiac aging.
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
ERC - Support for frontier research (ERC)Institución de acogida
60323 Frankfurt Am Main
Alemania