Biological Niches within Human Calcified Aortic Valves: Towards Understanding of the Pathological Biomineralization Process

Abstract

Despite recent advances, mineralization site, its microarchitecture, and composition in calcific heart valve remain poorly understood. A multiscale investigation, using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X-ray spectrometry (EDS), from micrometre up to nanometre, was conducted on human severely calcified aortic and mitral valves, to provide new insights into calcification process. Our aim was to evaluate the spatial relationship existing between bioapatite crystals, their local growing microenvironment, and the presence of a hierarchical architecture. Here we detected the presence of bioapatite crystals in two different mineralization sites that suggest the action of two different growth processes: a pathological crystallization process that occurs in biological niches and is ascribed to a purely physicochemical process and a matrix-mediated mineralized process in which the extracellular matrix acts as the template for a site-directed nanocrystals nucleation. Different shapes of bioapatite crystallization were observed at micrometer scale in each microenvironment but at the nanoscale level crystals appear to be made up by the same subunits.

Cell-matrix mechanics and pattern formation in inflammatory cardiovascular calcification

“…16 Both vascular and valvular calcification undergo a progressive maturation process with continuous changes in composition, similar to the multistep process of bone formation. 20 It is even conceivable that calcified vascular matrix undergoes the continuous remodelling process seen in bone. In human plaque, calcification takes on the form of mature trabecular bone tissue in 65% of femoral lesions and approximately 15% of carotid lesions and aortic valve nodules.…”

Aortic calcified particles modulate valvular endothelial and interstitial cells

“…Turbidity was able to gauge a measure of the particles and this was reproducible and consistent over different days and has been used with other calcified particles (14,18). The heterogeneity in the calcified particles has been linked to the physicochemical parameters of their native growth niche and to the local condition of the extracellular matrix (13).…”

“…Calcified particles from valves, coronary arteries and aortae had the same unique architecture, composition and crystallinity (10). Spherical and semispherical deposits together with lamellar crystals have also been shown in calcified valves (13). Immunolabelling of aortic valve tissues showed strong positive labelling for early osteoblastic transcription factors RUNX2 and Sp7 expression in cells near the spherical particles but no osteocalcin.…”

SEM BSE 3D Image Analysis of Human Incus Bone Affected by Cholesteatoma Ascribes to Osteoclasts the Bone Erosion and VpSEM dEDX Analysis Reveals New Bone Formation

“…Elemental mapping (Figure 8(b)) clearly shows the presence of calcium in matrix vesicles, while sulphur, contained in matrix proteoglycans, is present only in the surrounding extracellular matrix. Calcium and phosphorus are the characteristic elements of bioapatite [19][20][21]. The elemental mapping clearly demonstrates that matrix vesicles have a calcium phosphate content.…”