Projektbeschreibung
Neurovaskuläre Interaktionen im alternden Herzen
Das Risiko einer Beeinträchtigung der kardiovaskulären Gesundheit steigt mit zunehmendem Alter. Verschiedene Faktoren wie elektrophysiologische Veränderungen prädisponieren ältere Menschen für das Risiko von Herzrhythmusstörungen, aber es fehlen Informationen über die Mechanismen der altersbedingten pathophysiologischen Veränderungen. Das EU-finanzierte Projekt Neuroheart wird aufzeigen, dass eine Beeinträchtigung der neurovaskulären Schnittstelle im alternden Herzen für altersbedingte Krankheiten verantwortlich sein kann. Im Mittelpunkt stehen dabei die Axone des Herzens und die Rolle von Semaphorin 3a in den Endothelzellen des alternden Herzens sowie die verringerte Neuronendichte. Neuroheart wird die elektrische Stabilität und Herzrhythmusstörungen, das Nervensekretom und die Wechselwirkungen zwischen Neuronen und Gefäßen untersuchen, was zu einem besseren Verständnis der neurovaskulären Interaktionen im alternden Herzen führen wird.
Ziel
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.
Wissenschaftliches Gebiet
Programm/Programme
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thema/Themen
Finanzierungsplan
ERC - Support for frontier research (ERC)Gastgebende Einrichtung
60323 Frankfurt Am Main
Deutschland