AI Article Synopsis
- Human aortic valve interstitial cells (AVICs) from calcific aortic valve disease (CAVD) show increased fibrocalcific activity, and the study aims to uncover factors that promote this process.
- Proteomic analysis revealed elevated levels of cathepsin D in AVICs from diseased valves, leading to increased expression of fibrocalcification markers like Runx2 and collagen deposition when cathepsin D was introduced.
- The study concludes that elevated cathepsin D in diseased AVICs promotes fibrocalcification through the ERK1/2-Sox9 pathway, highlighting its potential role in the progression of CAVD.
Article Abstract
Background: Human Aortic valve interstitial cells (AVICs) from calcific aortic valve disease (CAVD)-affected valves exhibit elevated fibrocalcific activity although the underlying mechanism remains incompletely understood. This study aimed to identify endogenous factors that promote aortic valve fibrocalcification.
Methods And Results: Proteomic analysis found increased cathepsin D levels in AVICs from CAVD-affected valves compared to AVICs from normal valves, and this finding was validated by immunoblotting. ELISA assay identified exacerbated release of cathepsin D by AVICs of diseased valves. Recombinant human cathepsin D upregulated the expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), collagen I and collagen IV in human AVICs, resulting in the deposition of calcium and collagen. Blocking of the ERK1/2-Sox9 signaling pathway markedly reduced the pro-fibrocalcific effect of cathepsin D. Moreover, normal AVICs express and release greater levels of cathepsin D when exposed to soluble matrilin 2. Knockdown of cathepsin D attenuated the fibrocalcific response induced by soluble matrilin 2.
Conclusion: AVICs of diseased aortic valves produce and release greater levels of cathepsin D that exerts a pro-fibrocalcific effect on AVICs through the ERK1/2-Sox9 pathway. Soluble matrilin 2 up-regulates cathepsin D to elevate AVIC fibrocalcific activity. Over-expression of cathepsin D in the aortic valve may enhance the pathobiological activities in AVICs.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458440 | PMC |
| http://dx.doi.org/10.3389/fcvm.2024.1410862 | DOI Listing |
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