Physicochemical characterization of human cardiovascular deposits

  • George KuranovEmail author
  • Anton Nikolaev
  • Olga Frank-Kamenetskaya
  • Nicolay Gulyaev
  • Olga Volina
Original Paper


Detailed crystal chemical characterization of human pathological cardiovascular deposits (PCD) was conducted applying wide set of the instrumental methods (XRD, FTIR, Raman, SEM, different chemical analyses). There was some progress achieved in the understanding of it formation mechanism. The obtained data evidence that pathological cardiovascular deposits are presented by non-stoichiometric water-bearing B-type carbonated hydroxyapatite just like other apatites of the human body. But PCD apatite is characterized by higher concentration of B-type carbonate ion (up to ~ 6 wt%) which leads to the increasing influence of the carbonate-ion on the unit cell parameters in comparison with water and other substitutes. Another difference between PCD apatite and other pathogenic apatites of the human body is the smaller variations of the unit cell parameters, caused by smaller variations of the blood chemical composition. It was shown that apatite on the surface of PCD is characterized by the more non-stoichiometric composition compared to apatite inside these deposits. It is assumed that the formation mechanisms of the PCD apatite and the bone apatite may be similar.


Cardiovascular apatite X-ray diffraction IR spectroscopy/Raman spectroscopy X-ray spectroscopy (XPS/EDX) Electron microscopy 



The authors thank Dr. L.M. Lamanova for providing some samples of cardiovascular deposits. The instrumental investigations have been performed at the Research Resource Centers of St. Petersburg State University: Center for Geo-Environmental Research and Modelling (GEOMODEL), Chemical Analysis and Materials Research Center, Center for X-ray Diffraction Studies, Center for Physical Methods of Surface Investigation.


This work was partially supported by President of Russian Federation Grant for leading scientific schools (no. NSh-3079.2018.5).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The signed consents on taking PCD samples were obtained from either the patient or next of kin. All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments. The approval of the ethic committee of the S.M. Kirov Military Medical Academy for the study was obtained.


  1. 1.
    Elliott JC (1994) Structure and chemistry of the apatites and other calcium orthophosphates. Elsevier, AmsterdamGoogle Scholar
  2. 2.
    Dove PM, De Yoreo JJ, Weiner S (eds) (2003) Biomineralization. In: Reviews in mineralogy and geochemistry, vol 54. Mineralogical Society of America and Geochemical Society, Washington DC, USA, p 381Google Scholar
  3. 3.
    Frank-Kamenetskaya OV (2008) Crystal chemistry and synthesis of carbonate apatites—main minerals in living organisms. In: Conference paper: 9th international congress for applied mineralogy, ICAM 2008. Australasian Institute of Mining and Metallurgy Publication Series, Brisbane, Australia, pp 313–319Google Scholar
  4. 4.
    Rey C, Combes C (2016) Physical chemistry of biological apatites. In: Aparicio C, Ginebra M-P (eds) Biomineralization and biomaterials. Woodhead Publishing, Boston, pp 95–127CrossRefGoogle Scholar
  5. 5.
    Cottignoli V, Cavarretta E, Salvador L, Valfré C, Maras A (2015) Morphological and chemical study of pathological deposits in human aortic and mitral valve stenosis: a biomineralogical contribution. Pathol Res, IntGoogle Scholar
  6. 6.
    Epple M, Lanzer P (2001) How much interdisciplinarity is required to understand vascular calcifications? Formulation of four basic principles of vascular calcification. Z Kardiol 90:2–5CrossRefGoogle Scholar
  7. 7.
    Louvet L, Bazin D, Büchel J, Steppan S, Passlick-Deetjen J, Massy ZA (2015) Characterisation of calcium phosphate crystals on calcified human aortic vascular smooth muscle cells and potential role of magnesium. PLoS One 10:e0115342. CrossRefGoogle Scholar
  8. 8.
    Yahagi K, Kolodgie FD, Otsuka F, Finn AV, Davis HR, Joner M, Virmani R (2016) Pathophysiology of native coronary, vein graft, and in-stent atherosclerosis. Nat Rev Cardiol 13:79–98CrossRefGoogle Scholar
  9. 9.
    Becker A, Epple M, Müller KM, Schmitz I (2004) A comparative study of clinically well-characterized human atherosclerotic plaques with histological, chemical, and ultrastructural methods. J Inorg Biochem 98:2032–2038CrossRefGoogle Scholar
  10. 10.
    LeGeros RZ (2001) Formation and transformation of calcium phosphates: relevance to vascular calcification. Z Kardiol 90:116–124CrossRefGoogle Scholar
  11. 11.
    Tomazic BB (2001) Physicochemical principles of cardiovascular calcification. Z Kardiol 90:68–80CrossRefGoogle Scholar
  12. 12.
    Bonfield W, Gibson I (2002) Novel synthesis and characterization of an AB-type carbonate-substituted hydroxyapatite. J Biomed Mater Res 59:697–708CrossRefGoogle Scholar
  13. 13.
    Gilinskaya LG, Grigorieva TN, Okuneva GN, Vlasov YA (2003) Investigation of pathogenic mineralization on human heart valves. 1. Chemical and phase composition. J Struct Chem 44:622–631CrossRefGoogle Scholar
  14. 14.
    Gilinskaya LG, Okuneva GN, Vlasov YA (2003) Investigation of pathogenic mineralization on human heart valves. II. ESR spectroscopy. J Struct Chem 44:813–820CrossRefGoogle Scholar
  15. 15.
    Gilinskaya LG, Rudina NA, Okuneva GN, Vlasov YA (2003) Pathogenic mineralization on human heart valves. III. Electron microscopy. J Struct Chem 44:1038–1045CrossRefGoogle Scholar
  16. 16.
    Pigozzi F, Rizzo M, Fagnani F, Parisi A, Spataro A, Casasco M, Borrione P (2011) Endothelial (dys)function: the target of physical exercise for prevention and treatment of cardiovascular disease. J Sports Med Phys Fitness 51:260–267Google Scholar
  17. 17.
    Danilchenko SN, Kuznetsov VN, Stanislavov AS, Kalinkevich AN, Starikov VV, Moskalenko RA, Kalinichenko TG, Kochenko AV, Lü J, Shang J, Yang S (2013) The mineral component of human cardiovascular deposits: morphological, structural and crystal-chemical characterization. Cryst Res Technol 48:153–162CrossRefGoogle Scholar
  18. 18.
    Jono S, Shioi A, Ikari Y, Nishizawa Y (2006) Vascular calcification in chronic kidney disease. J Bone Miner Metab 24:176–181CrossRefGoogle Scholar
  19. 19.
    Kaden JJ, Bickelhaupt S, Grobholz R, Vahl CF, Hagl S, Brueckmann M, Haase KK, Dempfle CE, Borggrefe M (2004) Expression of bone sialoprotein and bone morphoeenetic protein-2 in calcific aortic stenosis. J Heart Valve Dis 13:560–566Google Scholar
  20. 20.
    Martel J, Young D, Young A, Wu CY, Chen CD, Yu JS, Young JD (2011) Comprehensive proteomic analysis of mineral nanoparticles derived from human body fluids and analyzed by liquid chromatography-tandem mass spectrometry. Anal Biochem 418:111–125CrossRefGoogle Scholar
  21. 21.
    Mohler Iii ER, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS (2001) Bone formation and inflammation in cardiac valves. Circulation 103:1522–1528CrossRefGoogle Scholar
  22. 22.
    Rajamannan NM, Subramaniam M, Rickard D, Stock SR, Donovan J, Springett M, Orszulak T, Fullerton DA, Tajik AJ, Bonow RO, Spelsberg T (2003) Human aortic valve calcification is associated with an osteoblast phenotype. Circulation 107:2181–2184CrossRefGoogle Scholar
  23. 23.
    Dweck MR, Boon NA, Newby DE (2012) Calcific aortic stenosis: a disease of the valve and the myocardium. J Am Coll Cardiol 60:1854–1863CrossRefGoogle Scholar
  24. 24.
    O’Neill WC (2007) Vascular calcification: not so crystal clear. Kidney Int 71:282–283CrossRefGoogle Scholar
  25. 25.
    Verberckmoes SC, Persy V, Behets GJ, Neven E, Hufkens A, Zebger-Gong H, Müller D, Haffner D, Querfeld U, Bohic S, De Broe ME, D’Haese PC (2007) Uremia-related vascular calcification: more than apatite deposition. Kidney Int 71:298–303CrossRefGoogle Scholar
  26. 26.
    Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin Iii JP, Guyton RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt Iii TM, Thomas JD (2014) 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American college of cardiology/American heart association task force on practice guidelines. J Am Coll Cardiol 63:2438–2488CrossRefGoogle Scholar
  27. 27.
    Li R, Chapman S, Thompson M, Schwartz M (2009) Developing a simple method to process bone samples prior to DNA isolation. Leg Med 11:76–79CrossRefGoogle Scholar
  28. 28.
    Solodyankina A, Nikolaev A, Frank-Kamenetskaya O, Golovanova O (2016) Synthesis and characterization of nanocrystalline apatites from solution modeling human blood. J Mol Struct 1119:484–489CrossRefGoogle Scholar
  29. 29.
    Fleet ME (2013) The carbonate ion in hydroxyapatite: recent X-ray and infrared results. Front Biosci (Elite Ed) 5:643–652CrossRefGoogle Scholar
  30. 30.
    Frank-Kamenetskaya O, Kol’tsov A, Kuz’mina M, Zorina M, Poritskaya L (2011) Ion substitutions and non-stoichiometry of carbonated apatite-(CaOH) synthesised by precipitation and hydrothermal methods. J Mol Struct 992:9–18CrossRefGoogle Scholar
  31. 31.
    Jastrzebski W, Sitarz M, Rokita M, Bulat K (2011) Infrared spectroscopy of different phosphates structures. Spectrochim Acta A 79:722–727CrossRefGoogle Scholar
  32. 32.
    Sun L, Chow LC, Frukhtbeyn SA, Bonevich JE (2010) Preparation and properties of nanoparticles of calcium phosphates with various Ca/P ratios. J Res Nat Inst Stand Technol 115:243–255CrossRefGoogle Scholar
  33. 33.
    Karampas IA, Kontoyannis CG (2013) Characterization of calcium phosphates mixtures. Vib Spectrosc 64:126–133CrossRefGoogle Scholar
  34. 34.
    Cölfen H, Antonietti M (2008) Mesocrystals and nonclassical crystallization. Wiley, Chichester, p 276. CrossRefGoogle Scholar
  35. 35.
    Harrington JM, Young DJ, Essader AS, Sumner SJ, Levine KE (2014) Analysis of human serum and whole blood for mineral content by ICP-MS and ICP-OES: development of a mineralomics method. Biol Trace Elem Res 160:132–142CrossRefGoogle Scholar
  36. 36.
    Moreno EC, Margolis HC (1988) Composition of human plaque fluid. J Dent Res 67:1181–1189CrossRefGoogle Scholar
  37. 37.
    Frank-Kamenetskaya OV, Izatulina AR, Kuz’mina MA (2016) Ion substitutions, non-stoichiometry, and formation conditions of oxalate and phosphate minerals of the human body. In: Frank-Kamenetskaya O, Panova E, Vlasov D (eds) Biogenic—abiogenic interactions in natural and anthropogenic systems. Lecture notes in earth system sciences. Springer, Cham, pp 425–442. CrossRefGoogle Scholar
  38. 38.
    Berezov TT, Korovin MA (2002) Biologicheskaya Himiya. Medicina, MoscowGoogle Scholar
  39. 39.
    Simon P, Rosseeva E, Buder J, Carrillo-Cabrera W, Kniep R (2009) Embryonic states of fluorapatite-gelatine nanocomposites and their intrinsic electric-field driven morphogenesis: the missing link on the way from atomistic simulations to pattern formation on the mesoscale. Adv Funct Mater 19:3596–3603CrossRefGoogle Scholar

Copyright information

© Society for Biological Inorganic Chemistry (SBIC) 2019

Authors and Affiliations

  1. 1.Saint Petersburg State UniversitySt. PetersburgRussia
  2. 2.I.V. Grebenshchikov Institute of Silicate Chemistry RASSt. PetersburgRussia
  3. 3.S.M. Kirov Military Medical AcademySt. PetersburgRussia

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