H2020Individual fellowship2019–2021

MechanoMVP · Mechanosensing and Mitral Valve Prolapse: from the Molecular Mechanisms to the Progression of the Disease

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration: 2019-05-01 → 2021-10-30
EU contribution: €196,708
Participants: 1
Scheme: MSCA-IF-EF-RI

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Results in brief

Mechanosensing and Mitral Valve Prolapse: from the Molecular Mechanisms to the Progression of the Disease

Mitral valve prolapse (MVP) is the most frequent form of degenerative mitral valve (MV) disease and is a major cause of cardiovascular morbidity and mortality. No medical therapy is currently available. Recent familial and population genetic studies have identified genes causally related to MVP, such as FLNA, encoding for Filamin A protein. These findings have paved the road to study mechanisms and signaling pathways involved in the development and progression of MVP that will then be useful to identify potential therapeutic targets and thus limit the use of cardiac surgery. This relies on two complementary approaches: comprehensive phenotyping of the FLNA-MVP patients and the implementation of experimental models. In the MechanoMVP project, I propose to identify and study the pathophysiological mechanisms and regulation of signaling pathways involved in the development and progression of MVP based on the comprehensive analysis of the unique knock-in rat model for FLNA-P637Q mutation recently developed at the host institution. Over the action, I generated landmark data in the field of MVP, by identifying main signaling pathways involved in the development of MVP (data currently submitted for publication). I pursued this work by studying one of the main pathways identified in order to dissect the specific pathophysiological mechanisms and identify potential therapeutic targets. In conclusion, the action provide unique validation of potential therapeutic targets, with important translational potential due the physiological and integrated models used in the project.

Data: CORDIS, © European Union

Project objective

Mitral valve prolapse (MVP) is the most frequent form of degenerative mitral valve (MV) disease and is a major cause of cardiovascular morbidity and mortality. No medical therapy is currently available. Familial and population genetic studies have identified genes causally related to non-syndromic MVP, such as FLNA, encoding for Filamin A protein. These findings have paved the road to study mechanisms and signaling pathways involved in the development and progression of MVP that will then be useful to identify potential therapeutic targets. This relies on two complementary approaches: a comprehensive phenotyping of the FLNA-MVP patients and the implementation of experimental models.In the MechanoMVP project, I propose to study stress-related mechanisms and regulation of signaling pathways involved in the development and progression of MVP based on the comprehensive analysis of the unique knock-in rat model for FLNA-P637Q mutation, as well as the related-cellular models, recently developed at the host institution. The specific actions I will conduct through this project are the comprehensive phenotyping of the unique rat model using multimodality imaging and biochemical approaches coupled with the cellular and molecular analyses done on mutant and WT valvular cell models. Based on this integrative approach mixing genetics, pathophysiological and mechanistic experimentations, and a multimodality/gold standard imaging phenotyping, MechanoMVP will provide landmark data in the field of MVP. In the context of a frequent CV pathology increasing with age and the rapid aging of the population, MVP and its ensuing adverse CV events will exponentially grow in the coming next years. With the only use of surgery to “treat” MVP patients, this disease will considerably increase the health care and socio-economic burden. MechanoMVP will open new avenues for the development of therapeutic approaches.

Original text from CORDIS.

Participants

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisCoordinatorFrance

MechanoMVP · Mechanosensing and Mitral Valve Prolapse: from the Molecular Mechanisms to the Progression of the Disease

Results in brief

Mechanosensing and Mitral Valve Prolapse: from the Molecular Mechanisms to the Progression of the Disease

Project objective

Participants

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