Project description
Long non-coding RNAs and age-associated cardiovascular diseases
Rising life expectancy correlates with the prevalence of age-induced cardiovascular diseases in the European Union. One of the age-associated cardiovascular diseases is heart failure with preserved ejection fraction (HFpEF), which is a complex condition involving different cell types and mechanisms leading to impaired relaxation of cardiomyocytes. The EU-funded NICCA project aims to study the molecular mechanisms behind intercellular communication and ageing resulting in HFpEF. Long non-coding RNAs (lncRNAs) are emerging as critical regulators of cellular functions and might contribute to ageing-induced cardiac dysfunction, including HFpEF. Understanding the role of lncRNAs in cardiac ageing and HFpEF will bring new therapeutic targets to attenuate age-induced cardiac dysfunction.
Objective
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.
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Funding Scheme
ERC-COG - Consolidator GrantHost institution
1081 HV Amsterdam
Netherlands