ArticleJournal of the American Heart Association2025
Contribution of the TRPM4 Channel to Osteogenic Differentiation of Human Aortic Valve Interstitial Cells.
Article in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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1 citing paper in PubMed.
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Authors and funding
13 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundAortic stenosis due to deleterious remodeling of the aortic valve is a health concern since it can be corrected only by valve replacement due to the poor knowledge of cellular mechanisms involved. Fibroblastic valvular interstitial cells (VICs) play a central role in valve leaflet stiffness by trans-differentiation into osteoblast-like cells leading to calcification. The TRPM4 (transient receptor potential melastatin 4) cation channel was shown to participate in cardiac fibroblast remodeling. It is also involved in radiation-induced aortic valve remodeling in vivo in mice. We hypothesized that TRPM4 might participate in human VIC transition to osteoblastic phenotype.
methodsHuman aortic valves were collected from patients undergoing surgical valve replacement. Isolated VICs were maintained 14 days in culture in standard or pro-calcifying media and submitted to the TRPM4 inhibitor 9-phenanthrol, or small hairpin RNA-TRPM4. Osteogenic differentiation was evaluated by measuring hydroxyapatite crystals by Alizarin red staining and protein expression of osteogenic markers.
resultsWestern blot on VICs revealed TRPM4 protein expression and channel functionality was confirmed by patch-clamp recordings exhibiting a cationic current sensitive to voltage and internal Ca
conclusionsTRPM4 participates in osteogenic differentiation of human VICs and thus appears as a target to prevent aortic valve remodeling.
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