The French National Research Agency Projects for science

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ANR funded project


Targeted LYmphatic and MIcrovessel Treatments in metabolic-DISease HFpEF

Heart Failure with preserved Ejection Fraction (HFpEF) represents a major unmet clinical need for
improved diagnostics, prognostics, and development of treatments to limit the morbimortality of this
increasingly common disease linked to metabolic syndrome (MetS). The objective of LYMIT-DIS is to
forward our understanding of the mechanisms involved in the cardiac diastolic dysfunction in HFpEF, with
the aim to identify and evaluate new tractable therapeutic targets.
In this integrated, multidisciplinary and translational project, we will evaluate the impact of MetS-induced
HFpEF, in a gender-dependent manner, in both experimental models and clinical cohorts. Our focus will be
to address the combined role of cardiac lymphatic and blood microvascular dysfunctions in mediating key
pathological steps such as cardiac blood supply/demand imbalance, edema, and inflammation, and their
effects on cardiac metabolism and fibrosis.
The key innovative aspects of our project are 1) investigations of the impact of MetS and gender on cardiac
lymphangiogenesis, angiogenesis, and microvascular glycocalyx remodeling; and 2) evaluations of the
roles of these processes in HFpEF pathogenesis. At the cellular level, we will determine how MetS alters
paracrine signalling in endothelial cells, macrophages, and fibroblasts vs. cardiomyocytes in search for new
molecular targets against diastolic dysfunction. Further, using cutting-edge technology, we will investigate if
insufficient cardiac perfusion and lymphatic transport in MetS modulate cardiac metabolism and fibrosis
thereby predisposing to HFpEF.







ANR grant: 240 697 euros
Beginning and duration: mars 2017 - 24 mois


ANR Programme: ERA-CVD (ERA-CVD) 2016

Project ID: ANR-16-ECVD-0004

Project coordinator:
Madame Ebba Brakenhielm (INSERM)


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The project coordinator is the author of this abstract and is therefore responsible for the content of the summary. The ANR disclaims all responsibility in connection with its content.