For the first time, whitlockite was identified as an independent mineral deposit in calcified aortic valves, challenging existing models of calcification.
The discovery of independent whitlockite formation in calcified aortic valves challenges existing calcification models and provides new insights into the pathophysiology of aortic stenosis.
Absolute Event Rate: 0% vs 0%
ABSTRACT Aortic valve stenosis (AS), the leading valvular disease in aging populations, is driven by complex extracellular matrix (ECM) modifications and progressive calcification. While intensive work has been done to describe the biomolecular progression of the disease, in‐depth characterization of the ECM, and in particular the soft tissue‐mineral interface is still lacking. This study employs Raman microscopy, a label‐free imaging technique, and transmission electron microscopy (TEM) to elucidate the biochemical and ultrastructural changes in stenotic aortic valves. High‐resolution spectroscopic imaging revealed distinct extracellular matrix modification across different regions, involving elastin degradation, cholesterol deposition, and mineral formation, comprising not only carbonated hydroxyapatite (cHAp) but also whitlockite. Elastin‐rich domains associated with cHAp deposition exhibited cross‐link degradation, while collagen matrices supported mineralized phases with varying mineral‐to‐matrix ratios that, in heavily mineralized regions, went far above those of mature human bone. For the first time, we demonstrated whitlockite as a mineral deposit in calcified aortic valves, in areas with different degrees of calcification. This implies that this Mg‐containing mineral, which has been considered a precursor to cHAp in pathological calcification, forms independently, challenging prevailing models of calcification. The combination of Raman and TEM showed how bone‐like cHAp mineralized collagen matrix in later stages engulfs the initial non‐physiological whitlockite deposits. This study advances our understanding of AS by capturing spatially resolved chemical and structural anomalies/tissue changes at the nanoscale. The findings highlight Raman microscopy's potential for probing calcification mechanisms across diverse tissue types and suggest its role in identifying novel therapeutic targets. This study underscores the value of integrative imaging methodologies in unraveling complex pathological processes and advancing patient care.
Meijden et al. (Sat,) reported a other. For the first time, whitlockite was identified as an independent mineral deposit in calcified aortic valves, challenging existing models of calcification.