Projektbeschreibung
Einfluss langer nicht-kodierender RNA auf altersbedingte Herz-Kreislauf-Erkrankungen
EU-weit besteht ein Zusammenhang zwischen steigender Lebenserwartung und Zunahme altersbedingter Herz-Kreislauf-Erkrankungen. Herzinsuffizienz mit erhaltener Ejektionsfraktion (heart failure with preserved ejection fraction, HFpEF) ist eine komplexe altersbedingte Herzerkrankung unter Beteiligung verschiedenster Zelltypen und Mechanismen, die die vollständige Relaxation des Herzmuskels verhindert. Schwerpunkte des EU-finanzierten Projekts NICCA sind die molekularen Mechanismen interzellulärer Kommunikation und altersbedingter HFpEF. Lange nicht-kodierende RNA (long non-coding RNA, lncRNA) sind offenbar kritische Regulatoren zellulärer Funktionen und könnten altersbedingte Herzfehlfunktionen wie HFpEF begünstigen. Ist der Beitrag von lncRNA zu Herzalterung und HFpEF genauer erforscht, sollen daraus neue therapeutische Zielstrukturen zur Behandlung altersbedingter Herzfehlfunktionen hervorgehen.
Ziel
Life expectancy in the European Union is rising and the prevalence of age-induced cardiovascular disease increases concomitantly. The main clinical presentation of age-induced cardiovascular disease is heart failure with preserved ejection fraction (HFpEF). HFpEF is a complex disease involving different cell types and mechanisms that contribute to impaired relaxation of cardiomyocytes. Currently there is no appropriate treatment for HFpEF. This proposal aims to better understand the molecular mechanisms behind intercellular communication and ageing that lead to HFpEF.
Long non-coding RNAs (lncRNAs) are emerging as novel key regulators of cellular functions and we hypothesize that lncRNAs contribute to ageing-induced cardiac dysfunction, including HFpEF. Preliminary experiments show that several long non-coding RNAs (lncRNAs) are differentially regulated during cardiac ageing, including the cardiomyocyte-enriched lncRNA Sarrah that is essential for cardiomyocyte survival. We propose to extensively characterize the role of Sarrah in HFpEF and to identify other lncRNAs that are involved in cardiac ageing. Importantly, we will focus those lncRNAs that are also affected in a cohort of human HFpEF patients. Furthermore, since disturbed intercellular communication is a hallmark of both ageing and HFpEF, we will identify lncRNAs that regulate endothelial cell-cardiomyocyte crosstalk. We will use state-of-the-art in vitro and in vivo models to assess cardiac ageing and function upon gain-of-function and loss-of-function of lncRNAs in a cell-type specific manner.
Understanding the role that Sarrah and other lncRNAs play in cardiac ageing and HFpEF will highlight novel potential therapeutic targets to attenuate age-induced cardiac dysfunction and will increase our knowledge of the underlying mechanisms controlling intercellular communication and cardiac function.
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
1081 HV Amsterdam
Niederlande