Arterial and Aortic Valve Calcification Abolished by Elastolytic Cathepsin S Deficiency in Chronic Renal Disease
Authors
Discussion
Loading...
Member takes
Implication
Animal study demonstrates that cathepsin S deficiency abolishes cardiovascular calcification in chronic renal disease, suggesting a novel therapeutic target.
Key Points
- To determine whether cathepsin S-mediated elastolysis accelerates arterial and aortic valve calcification in an animal model of chronic renal disease.
- Induced chronic renal disease (CRD) via 5/6 nephrectomy in apolipoprotein E-deficient mice with (apoE-/-/catS+/+, n=24) or without cathepsin S (apoE-/-/catS-/-, n=24), alongside control groups.
- Tracked in vivo cathepsin S activity and osteogenesis using dual molecular imaging probes 10 weeks post-nephrectomy.
- Quantified elastin fragmentation and calcium deposition via histology, and analyzed vascular smooth muscle cell calcification in vitro following elastin peptide and recombinant cathepsin S exposure.
- Molecular imaging and quantitative histology revealed marked osteogenic activity, elastin fragmentation, and calcification in aortas and aortic valves of CRD catS-expressing mice, which were substantially diminished in catS-deficient mice.
- Cathepsin S deletion did not trigger compensatory RNA upregulation of alternative elastolytic cathepsins or matrix metalloproteinases.
- Elastin peptides and recombinant cathepsin S directly increased vascular smooth muscle cell calcification in vitro, an effect further elevated under phosphate-enriched conditions.
Cite This Study
Aïkawa et al. (2009) studied this question.