Nanoscale characterisation of cardiovascular tissue calcification

Cardiovascular calcification contributes to the 17 million deaths globally caused by cardiovascular diseases. It is found in atherosclerotic plaques and remains one of the leading causes of valve stenosis. The only viable treatment for this disease remains the replacement of the tissue via surgical intervention. Recently, Bertazzo et al. showed the presence of nano/micro calcified particles in calcified heart tissues, as an early calcified structure that could be detected in the vascular tissue. With the recent discovery of the cardiovascular calcified particles, only little is known about their structure and composition. By combining state-of-the-art nano-analytical electron microscopy characterisation techniques, the work in the thesis shows the presence of two types of particles within the population of cardiovascular calcified particles. These two types of particles are composed of either apatite or whitlockite mineral with a different structure and crystallinity, suggesting at least two kinds of biomineralisation process leading to their formation. Using electron energy loss spectroscopy and atom probe tomography, the work in the thesis further unveils the presence of organic material, possibly protein in nature, within the mineralised structure of the calcified particles suggesting a biological process in their formation. More importantly, using a novel approach of in situ nano compression inside a scanning electron microscope, the work has also deduced the presence of nanogranules within the whitlockite particles, which shows a single crystal structure under diffraction studies. These results suggest that whitlockite particles have a mesocrystalline structure. To the best of our knowledge, this is also the first study to show the existence of whitlockite mesocrystals. Finally, the work reports the presence of whitlockite particles in different species of amniotes, providing clues to a possible common biomineralisation process in amniotes and a unified model of cardiovascular calcification.Open Acces