FFC Mac-In-MVP - Romain Capoulade (2023-2025)

Mitral valve dystrophy (MVD) is one of the most common valvular heart diseases affecting 2 to 5% of the population. Myxomatous MVD the main etiology observed in patients with mitral regurgitation associated with MV prolapse. To date, little is known about the mechanisms leading to MVD and there is no treatment available. The only remaining option is to repair or replace the diseased valve via open-heart surgery.

We have previously generated a unique knock-in (KI) rat model carrying the FlnA-P637Q mutation associated with MVD in humans and demonstrated that KI rats develop MVD with similar features to those in humans. Based on a transcriptomic analysis, we reported the involvement of multiple pathophysiological processes including extracellular matrix remodeling, epithelial cell migration, mechanotransduction, as well as a central role for immune cells. Indeed, 30% of the GO-terms differentially expressed in mutated valves as compared to control valves referred to pathways involved in myeloid cell activation. Preliminary data confirmed the abundance of macrophages in diseased valves.

Objective:

The main objective of the Mac-in-MVD project is to dissect the specific role of macrophages in the initiation and/or progression of MVD. This project will provide landmark data on mechanisms leading to this disturbing disease and open the way to identify therapeutic target.