Macrophage recruitment is a hallmark of non-syndromic myxomatous mitral valve disease
Abstract
Aims : Myxomatous mitral valve disease (MMVD) is a progressive cardiac disease characterized by extracellular matrix remodelling, leaflet thickening, and proteoglycan accumulation. Despite its significant contribution to cardiovascular morbidity and mortality, the underlying pathophysiological mechanisms involved in its development and progression remain unclear. Recent investigations have revealed a genetic component to the disease, such as mutations in the FLNA gene, and suggested potential involvement of immune cells in the pathogenesis of MMVD. In this study, we investigated the role of macrophages in MMVD using a large collection of human non-syndromic MMVD samples and a unique animal model, the Filamin-A knock-in (KI) rat. Methods and results : Transciptomic analysis of 78 human non-syndromic MMVD samples revealed significant enrichment of pathways associated with immune activation and macrophage recruitment. Comparative analyses between human and rat MMVD identified shared molecular signatures, validating the Filamin-A KI rat model for studying human MMVD pathophysiology. Analyses of wild-type (WT) and KI rat MVs demontrated a gradual activation of valvular cells from birth, which translated into phenotypic MV remodelling by postnatal day 7. These early events were associated with the development of a pro-inflammatory valvular environment, despite no initial increase in myeloid cells. The subsequent accumulation of macrophages in the already remodelled MV leaflets indicated the initiation of an active recruitment process, likely involved in the progression of non-syndromic MMVD. Conclusion : This study highlights the central role of chemotaxis and macrophage recruitment and activation in the pathophysiological processes leading to non-syndromic MMVD. Macrophage involvement emerges as a hallmark of non-syndromic MMVD, a disease previously described as non-inflammatory, and opens new avenues to identify potential therapeutic targets to mitigate disease progression.
Related
- Galectin-3 recruitment at the Mycobacterium tuberculosis -containing phagosome is critical in macrophage but dispensable in epithelial cells
- Algorithmic Multi-Domain Syndromic Profiling in Cerebrovascular Disease: A Deterministic Approach to Post-Stroke Neurocognitive Deficit Mapping
- An integrated human forebrain organoid reveals microglia-mediated CD8⁺ T cell recruitment and neuroimmune dysfunction in Alzheimer's disease pathology.
- CD13 expression in B cell malignancies is a hallmark of plasmacytic differentiation.
- Mapping intestinal microenvironment heterogeneity in Hirschsprung's disease by spatial transcriptomics: Role of THBS1 in macrophage polarization and neural stem cell regulation.
BibTeX
@article{vely2026macrophage,
title = {{Macrophage recruitment is a hallmark of non-syndromic myxomatous mitral valve disease}},
author = {Benjamin Le Vely and Constance Delwarde and Claire Toquet and Pascal Aumond and Nelli Blank-Stein and Emilie Charon and Séverine Rémy and Ignacio Anegon and Veronika Myasoedova and Vincenza Valerio and Paolo Poggio and Solena Le Scouarnec and Jean-Jacques Schott and Thierry Le Tourneau and Jean Merot and Elvira Mass and Romain Capoulade},
journal = {Cardiovascular Research},
year = {2026},
month = jun,
doi = {10.1093/cvr/cvag132},
url = {https://inserm.hal.science/inserm-05687495v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Macrophage recruitment is a hallmark of non-syndromic myxomatous mitral valve disease
AU - Benjamin Le Vely
AU - Constance Delwarde
AU - Claire Toquet
AU - Pascal Aumond
AU - Nelli Blank-Stein
AU - Emilie Charon
AU - Séverine Rémy
AU - Ignacio Anegon
AU - Veronika Myasoedova
AU - Vincenza Valerio
AU - Paolo Poggio
AU - Solena Le Scouarnec
AU - Jean-Jacques Schott
AU - Thierry Le Tourneau
AU - Jean Merot
AU - Elvira Mass
AU - Romain Capoulade
PY - 2026
DA - 2026/06/23
JO - Cardiovascular Research
DO - 10.1093/cvr/cvag132
UR - https://inserm.hal.science/inserm-05687495v1
AB - Aims : Myxomatous mitral valve disease (MMVD) is a progressive cardiac disease characterized by extracellular matrix remodelling, leaflet thickening, and proteoglycan accumulation. Despite its significant contribution to cardiovascular morbidity and mortality, the underlying pathophysiological mechanisms involved in its development and progression remain unclear. Recent investigations have revealed a genetic component to the disease, such as mutations in the FLNA gene, and suggested potential involvement of immune cells in the pathogenesis of MMVD. In this study, we investigated the role of macrophages in MMVD using a large collection of human non-syndromic MMVD samples and a unique animal model, the Filamin-A knock-in (KI) rat. Methods and results : Transciptomic analysis of 78 human non-syndromic MMVD samples revealed significant enrichment of pathways associated with immune activation and macrophage recruitment. Comparative analyses between human and rat MMVD identified shared molecular signatures, validating the Filamin-A KI rat model for studying human MMVD pathophysiology. Analyses of wild-type (WT) and KI rat MVs demontrated a gradual activation of valvular cells from birth, which translated into phenotypic MV remodelling by postnatal day 7. These early events were associated with the development of a pro-inflammatory valvular environment, despite no initial increase in myeloid cells. The subsequent accumulation of macrophages in the already remodelled MV leaflets indicated the initiation of an active recruitment process, likely involved in the progression of non-syndromic MMVD. Conclusion : This study highlights the central role of chemotaxis and macrophage recruitment and activation in the pathophysiological processes leading to non-syndromic MMVD. Macrophage involvement emerges as a hallmark of non-syndromic MMVD, a disease previously described as non-inflammatory, and opens new avenues to identify potential therapeutic targets to mitigate disease progression.
SN - 0008-6363
ER -