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.
Highlights
Calcific aortic valve stenosis (CAVS) is an important public health problem and represents the most common form of valvular heart disease in the industrialized countries [1]
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 matrixmediated mineralized process in which the extracellular matrix acts as the template for a site-directed nanocrystals nucleation
Starting from a micrometer-scale and using scanning electron microscopy (SEM) for biological specimen techniques [14, 17] we highlighted the presence of biological niches within the calcified extracellular matrix, very similar to vugs, small, unfilled cavities inside rock that may be formed through a variety of processes
Summary
Calcific aortic valve stenosis (CAVS) is an important public health problem and represents the most common form of valvular heart disease in the industrialized countries [1]. It is strictly associated with the formation of ectopic calcifications within aortic valve leaflets that interfere with cusps opening and lead to ventricular outflow obstruction [2] causing important clinical consequences in terms of mortality and morbidity [3]. Despite much effort devoted to unveil the molecular mechanisms leading to valve calcification, comprehension of the exact process remains uncertain. The calcific deposit within human valve tissue is constituted by a nonstoichiometric apatite, containing high carbonate (CO32−) content, from 5% to 10% in weight, and AB-type substitutions in apatite lattice [5, 6], as we previously reported; it is often indicated as “carbonate apatite” or more
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