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Abstract 4139829: New Insights in Non-syndromic Mitral Valve Dystrophy: Role of Inflammation and Macrophages

Title: Abstract 4139829: New Insights in Non-syndromic Mitral Valve Dystrophy: Role of Inflammation and Macrophages
Authors: Le Vely, Benjamin; Delwarde, Constance; toquet, claire; Aumond, Pascal; Charon, Emilie; Remy, Séverine; Anegon, Ignacio; Le Scouarnec, Solena; Schott, Jean-Jacques; Le Tourneau, Thierry; Mass, Elvira; Merot, Jean; Capoulade, Romain
Source: Circulation ; volume 150, issue Suppl_1 ; ISSN 0009-7322 1524-4539
Publisher Information: Ovid Technologies (Wolters Kluwer Health)
Publication Year: 2024
Description: Background: Myxomatous mitral valve dystrophy (MVD) is the first cause of mitral valve prolapse (MVP), a common disease affecting 2 to 3 % of the population. The first causal mutation in the FLNA gene (FLNA-P637Q), was associated with MVD in 2007. Recently, the FlnA-P637Q KI rat model was generated and phenotyped. Using multimodality imaging, MVD was diagnosed as early as 3 weeks (D21) and signature of chemotaxis and immune cell migration was described at the transcriptomic level. Aims: This study aims to delineate the contribution of macrophages recruitment and activation to the pathophysiology of MVD. Methods: New-born (D0), two days (D2) and seven days (D7) KI and WT animals were phenotyped. Anatomopathological score was used to assed MV morphological alterations. MV cell proportions were analyzed by flow cytometry (D7 and D21), and molecular phenotyping was done by bulk RNAseq (D7). WT and KI MVs were dissociated for valvular interstitial cells (VICs) primary culture and subsequent in vitro studies. Results: At D21, a 2-fold increased proportion of myeloid cells in KI MV compared to WT was detected by flow cytometry (13% vs 7%, p0.05), MV remodeling, characteristic of MVD, was observed and quantified at D7 (histological score: 7 in KI vs 4 in WT; p
Document Type: article in journal/newspaper
Language: English
DOI: 10.1161/circ.150.suppl_1.4139829
Availability: https://doi.org/10.1161/circ.150.suppl_1.4139829; https://journals.lww.com/10.1161/circ.150.suppl_1.4139829
Accession Number: edsbas.66914B6A
Database: BASE