Immune response as a new player in mitral valve prolapse

Mitral valve prolapse (MVP) affects 3% of the population and is characterized by a myxomatous MV remodeling. The pathophysiological mechanisms involved in MVP remain elusive and the only therapeutic option is to perform MV surgery. The first causing mutation in MVP has been identified on the FLNA gene. We recently generated a KI rat for the FLNA-P637Q mutation that develops MVP. A recent RNA-seq analysis revealed an upregulation of genes involved in immune response and inflammation pathways in the valves of KI rats compared to WT. The aim of this study was then to identify and quantify the immune cells present in MVs and assess their role in the development and/or progression of the disease. Flow cytometry was used to quantify the hematopoietic cells (CD45), resident macrophages (CD206), myeloid lineage (CD11b), endothelial progenitors (CD34) and endothelial cells (CD31) in the MV of 3-weeks old KI and WT rats. The location of those cells within the MV tissues was analysed by immunofluorescence on cryosectioned MVs. Cytometry results showed a higher proportion of CD45+ and CD206+ cells in the KI rats compared to WT (20% vs. 14% and 28% vs. 16%, respectively) but similar proportion of CD31+ (14%). The CD45 and CD206 immunofluorescences performed on WT animals showed a clear localization of the positive cells on the edge of the atrial side of the leaflet, in the sub-endothelium layer. In KI rats, CD45+ and CD206+ cells were diffusely located: close to the atrial side of the MV leaflet, but also into the medial third of the leaflet. This preliminary study showed that recruitment of immune cells in MVP could be an important player in the pathophysiological process leading the disease. To elucidate the specific roles of this pathway, the temporal recruitment of immune cells and their specific activity need to be studied over the course of the disease progression.