The accumulation of calcified material in cardiovascular tissue is thought to involve cytochemical, extracellular matrix and systemic signals; however, its precise composition and nanoscale architecture remain largely unexplored. Using nano-analytical electron microscopy techniques, we examined valves, aortae and coronary arteries from patients with and without calcific cardiovascular disease and detected spherical calcium phosphate particles, regardless of the presence of calcific lesions. We also examined lesions after sectioning with a focused ion beam and found that the spherical particles are composed of highly crystalline hydroxyapatite that crystallographically and structurally differs from bone mineral. Taken together, these data suggest that mineralized spherical particles may play a fundamental role in calcific lesion formation. Their ubiquitous presence in varied cardiovascular tissues and from patients with a spectrum of diseases further suggests that lesion formation may follow a common process. Indeed, applying materials science techniques to ectopic and orthotopic calcification has great potential to lend critical insights into pathophysiological processes underlying calcific cardiovascular disease.
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S.B. was supported by the Rosetrees Trust and the Junior Research Fellowship scheme at Imperial College London. E.G. was supported by a fellowship from the Wellcome Trust. K.L.C. was supported by a studentship from the British Heart Foundation Centre of Research Excellence at Imperial College London. M.M.S. gratefully acknowledges financial support from the Rosetrees Trust. We would like to thank K. Nitiputri for providing the murine osteoblast cells line MC3T3-E1. We would like to acknowledge the provision of preliminary animal tissues by W. Jahnen-Dechent and A. Kinkeldey.
The authors declare no competing financial interests.
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Bertazzo, S., Gentleman, E., Cloyd, K. et al. Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification. Nature Mater 12, 576–583 (2013). https://doi.org/10.1038/nmat3627
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