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Updated: Aug 27, 2025
Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification
Published on: November 20, 2017
Modulation of inflammatory M1-macrophages phenotype by valvular interstitial cells
Madjid Tagzirt1, Mickael Rosa1, Delphine Corseaux1
1University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
Background:
Aortic valve stenosis involves inflammation, excess deposition of a collagen-rich extracellular matrix, and calcification. Recent studies have shown that M1 or inflammatory macrophages derived from infiltrating monocytes promote calcification of valvular interstitial cells, the most prevalent cell type of the aortic valve. We hypothesized that valvular interstitial cells could modulate inflammatory macrophages phenotype.
Methods:
We first assessed macrophage phenotype in human aortic valve stenosis and control aortic valves from donors. Then, we examined profibrotic and inflammatory-related gene expression in valves and valvular interstitial cells. Finally, we investigated whether valvular interstitial cells can modify the phenotype of inflammatory macrophages.
Results:
Circulating monocytes and plasma transforming growth factor beta-1 levels of patients with aortic valve stenosis were significantly higher compared with patients without aortic valve stenosis. Histologic analysis of thickened spongiosa of the aortic valve from patients with aortic valve stenosis showed a high macrophage infiltration but a low matrix metalloproteinase-9 expression compared with control aortic valves. On the other hand, valvular interstitial cell culture of aortic valve stenosis exhibited a profibrotic phenotype with a high expression of transforming growth factor beta-1 and transforming growth factor beta-1/transforming growth factor beta-3 ratio but a decreased expression of the peroxisome proliferator-activated receptor gamma nuclear receptor. Valvular interstitial cell-conditioned media of aortic valve stenosis led to a decrease in enzymatic activity of matrix metalloproteinase-9 and an increase in production of collagen in inflammatory macrophages compared with valvular interstitial cell-conditioned media from control aortic valve donors.
Conclusions:
These findings indicate that profibrotic valvular interstitial cells promote the imbalance of extracellular matrix remodeling by reducing matrix metalloproteinase-9 production on inflammatory macrophages that lead to excessive collagen deposition observed in aortic valve stenosis. Further investigation is needed to clarify the role of transforming growth factor beta-1/proliferator-activated receptor gamma nuclear receptor/matrix metalloproteinase-9 in aortic valve stenosis.
Insights
Profibrotic valvular interstitial cells in aortic valve stenosis reduce matrix metalloproteinase-9 in macrophages, leading to excess collagen. Further research is needed on TGF-β1/PPARγ/MMP-9 roles.
Area of Science:
- Cardiovascular Biology
- Cellular Biology
- Pathology
Background:
- Aortic valve stenosis is characterized by inflammation, extracellular matrix deposition, and calcification.
- Inflammatory M1 macrophages promote valvular interstitial cell calcification.
- Valvular interstitial cells' role in modulating macrophage phenotype is unexplored.
Purpose of the Study:
- To assess macrophage phenotype in human aortic valve stenosis.
- To examine gene expression related to fibrosis and inflammation in valves and valvular interstitial cells.
- To determine if valvular interstitial cells can alter inflammatory macrophage phenotype.
Main Methods:
- Assessed macrophage phenotype in human aortic valve stenosis and control valves.
- Examined profibrotic and inflammatory gene expression in valves and valvular interstitial cells.
- Investigated valvular interstitial cell influence on inflammatory macrophage phenotype.
Main Results:
- Patients with aortic valve stenosis had higher circulating monocytes and plasma TGF-β1.
- Aortic valve stenosis valves showed high macrophage infiltration and low MMP-9.
- Valvular interstitial cells from aortic valve stenosis exhibited a profibrotic phenotype (high TGF-β1, low PPARγ).
- Valvular interstitial cell-conditioned media from aortic valve stenosis decreased MMP-9 activity and increased collagen in macrophages.
Conclusions:
- Profibrotic valvular interstitial cells contribute to aortic valve stenosis by reducing MMP-9 in macrophages, causing excessive collagen deposition.
- Further research is required to elucidate the roles of TGF-β1/PPARγ/MMP-9 in aortic valve stenosis pathogenesis.
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