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Spermidine in hypertension: therapeutic potential and novel mechanisms

Project description

Spermidine: a new medication against hypertension?

Hypertension is a leading cause of cardiovascular disease, with only one third of patients achieving efficient blood pressure control with existing medications. Accumulating evidence indicates that spermidine, an endogenous activator of autophagy and dietary supplement, correlates with lower blood pressure in humans. The EU-funded SPeR-ToNE project will capitalise on this observation to provide insight into the mechanism by which spermidine counteracts hypertension. Researchers will apply a multitude of cutting-edge techniques, animal models and human samples to study the cross-talk between blood pressure control and autophagy. Results will pave the way towards the development of novel interventions against hypertension.

Objective

Hypertension pharmacotherapy, albeit fairly effective, is far from ideal and adequate blood pressure control is only achieved in one third of patients. As such, hypertension is still the global leading cause of cardiovascular disease and mortality. In this regard, we have recently discovered that higher intake of the caloric restriction mimetic spermidine – a potent inducer of the cellular quality control mechanism, autophagy – correlates with lower blood pressure in humans. Administering spermidine to animals also delays the development of hypertension and vascular aging, suggesting it might be useful for disease prevention. However, whether spermidine can be used for therapy, as urgently needed in patients, is still unknown. Thus, the main objective of this proposal is to elucidate the therapeutic benefit of spermidine in established experimental hypertension. Applying a multitude of cutting-edge techniques, including knockout of autophagy genes and metabolic flux, we will provide key mechanistic insights on whether spermidine counteracts hypertension via activating autophagy, upregulating the arginine-nitric oxide axis, or both. With the ultimate goal of translating our findings from animals to humans, we will validate the clinical relevance of these mechanisms in patients' samples. Hence, this proposal will not only reveal a potential novel treatment for patients with hypertension, but will also study a previously understudied cross-talk between blood pressure control and autophagy. If true, we anticipate the project results to pave the way for a novel concept for hypertension therapy. Considering that the work will be done at a leading multi-disciplinary research group, where the researcher will bring expertise in cardiology and receive advanced training in cell biology and molecular metabolism, the fellowship will substantially advance his academic career to eventually reach his goal of leading his own research team.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

INSTITUT GUSTAVE ROUSSY
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 196 707,84
Address
Rue Camille Desmoulins 39
94805 Villejuif
France

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Region
Ile-de-France Ile-de-France Val-de-Marne
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 196 707,84
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