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Vascular cemeteries formed by biological nanoparticles

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Abstract

We report the discovery of dense colonies of globular structures ranging from 100 nm to 5 μm in the tunica media of the femoral artery of an 89-year-old female cadaver. Systematic analysis using scanning electron microscopy, energy dispersive X-ray spectroscopy and light microscopy reveals that the globular structures are surrounded by vascular smooth muscle cells (VSMCs) and consist predominantly of calcium phosphate. Inspection of the images suggests the action of two complementary growth processes. The structures may grow both in size and in number locally by Ostwald ripening and a replicative route, respectively. Morphology in conjunction with the quality of their native growth niche suggests that they are different from nanocrystals released from apoptotic bodies. Their tendency to fill VSMC pockets leads to the speculation that they could represent an effort of the VSMC system to wall off cytotoxic nanocrystals liberated from apoptotic bodies. Alternatively, the structures may be equivalent with nanobacteria (NB)—a nomenclature which caused confusion. This is reflected by the multitude of names used by different authors for the nanoentities (living nanovesicles, nanobionta, calcifying nanoparticles, and nanons). Indeed, there is no clear definition in the literature as to what NB are. Considering that the calcium phosphate nanoparticles have been identified in the human body, we used in our study the descriptive name biological nanoparticles—the world’s first nanoparticles.

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References

  • Al-Aly Z (2011) Phosphate, oxidative stress, and nuclear factor-κB activation in vascular calcification. Kidney Int 79:1044–1047

    Article  CAS  Google Scholar 

  • Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S (2004) Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431:805–810

    Article  CAS  Google Scholar 

  • Baker M (2012) Cancer stem cells tracked. Nature 488:13–14

    Article  CAS  Google Scholar 

  • Bertelsen S (1961) Hexosamine, hydroxyproline and calcium levels in the tunica media of the human aorta and pulmonary artery. Acta Pharmacol Toxicol (Copenh) 18:359–369

    Article  CAS  Google Scholar 

  • Candemir B, Ertas FS, Kaya CT, Ozdol C, Hasan T, Akan OA, Sahin M, Erol C (2010) Association between antibodies against calcifying nanoparticles and mitral annular calcification. J Heart Valve Dis 19:745–752

    Google Scholar 

  • Canton I, Battaglia G (2012) Endocytosis at the nanoscale. Chem Soc Rev 41:2718–2739

    Article  CAS  Google Scholar 

  • Chen Q, Shen X (2010) Formation of mesoporous BaSO4 microspheres with a larger pore size via Ostwald ripening at room temperature. Cryst Growth Des 10:3838–3842

    Article  CAS  Google Scholar 

  • Chen L, Huang XB, Xu QQ, Li JX, Jia XJ, Wang XF (2010) Cultivation and morphology of nanobacteria in sera of patients with kidney calculi. Beijing Da Xue Xue Bao 42:443–446

    Google Scholar 

  • Cisar JO, Xu DQ, Thompson J, Swaim W, Hu L, Kopecko DJ (2000) An alternative interpretation of nanobacteria-induced biomineralization. Proc Natl Acad Sci USA 97:11511–11515

    Article  CAS  Google Scholar 

  • Drancourt M, Jacomo V, Lépidi H, Lechevallier E, Grisoni V, Coulange C, Ragni E, Alasia C, Dussol B, Berland Y, Raoult D (2003) Attempted isolation of Nanobacterium sp. microorganisms from upper urinary tract stones. J Clin Microbiol 41:368–372

    Article  Google Scholar 

  • Ewence AE, Bootman M, Roderick HL, Skepper JN, McCarthy G, Epple M, Neumann M, Shanahan CM, Proudfoot D (2008) Calcium phosphate crystals induce cell death in human vascular smooth muscle cells: a potential mechanism in atherosclerotic plaque destabilization. Circ Res 103:e28–e34

    Article  CAS  Google Scholar 

  • Franiczek R, Szufnarowski K, Czarny A, Zaczynska E, Krzyzanowska B, Hauser W, Mokracka-Latajka G (2009) Occurrence of calcifying nanoparticles in clinical specimens derived from patients with atherosclerosis and nephrolithiasis. Adv Clin Exp Med 18:269–275

    Google Scholar 

  • Guo Y, Zhang D, Lu H, Luo S, Shen X (2012) Association between calcifying nanoparticles and placental calcification. Int J Nanomed 7:1679–1686

    Article  CAS  Google Scholar 

  • Heiss A, DuChesne A, Denecke B, Grötzinger J, Yamamoto K, Renné T, Jahnen-Dechent W (2003) Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles. J Biol Chem 278:13333–13341

    Article  CAS  Google Scholar 

  • Hogan J (2004) Nanobacteria revelations provoke new controversy. N Sci. http://www.newscientist.com/article/dn5009-nanobacteria-revelations-provoke-new.controversy. Accessed 19 May 2004

  • Jelic TM, Chang HH, Roque R, Malas AM, Warren SG, Sommer AP (2007) Nanobacteria-associated calcific aortic valve stenosis. J Heart Valve Dis 16:101–105

    Google Scholar 

  • Kim BY, Rutka JT, Chan WC (2010) Nanomedicine. N Engl J Med 363:2434–2443

    Article  CAS  Google Scholar 

  • Kutikhin AG, Brusina EB, Yuzhalin AE (2012) The role of calcifying nanoparticles in biology and medicine. Int J Nanomed 7:339–350

    Article  CAS  Google Scholar 

  • Martel J, Young JD (2008) Purported nanobacteria in human blood as calcium carbonate nanoparticles. Proc Natl Acad Sci USA 105:5549–5554

    Article  CAS  Google Scholar 

  • Martel J, Wu CY, Young JD (2010) Critical evaluation of gamma-irradiated serum used as feeder in the culture and demonstration of putative nanobacteria and calcifying nanoparticles. PLoS ONE 5:e10343

    Article  Google Scholar 

  • 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 418:111–125

    Article  CAS  Google Scholar 

  • Martel J, Young D, Peng HH, Wu CY, Young JD (2012) Biomimetic properties of minerals and the search for life in the Martian meteorite ALH84001. Annu Rev Earth Planet Sci 40:167–193

    Article  CAS  Google Scholar 

  • Massy ZA, Mentaverri R, Mozar A, Brazier M, Kamel S (2008) The pathophysiology of vascular calcification: are osteoclast-like cells the missing link? Diabetes Metab 34(Suppl 1):S16–S20

    Article  Google Scholar 

  • Miller VM, Rodgers G, Charlesworth JA, Kirkland B, Severson SR, Rasmussen TE, Yagubyan M, Rodgers JC, Cockerill FR III, Folk RL, Rzewuska-Lech E, Kumar V, Farell-Baril G, Lieske JC (2004) Evidence of nanobacterial-like structures in calcified human arteries and cardiac valves. Am J Physiol Heart Circ Physiol 287:H1115–H1124

    Article  CAS  Google Scholar 

  • Moore PB (2011) How small is small? A biophysical chemists thoughts about the lower limits of cell sizes. In: Luisi PL, Stano P (eds) The minimal cell. Springer, Dordrecht, pp 65–71

    Chapter  Google Scholar 

  • Myakishev-Rempel M, Stadler I, Brondon P, Axe DR, Friedman M, Nardia FB, Lanzafame R (2012) A preliminary study of the safety of red light phototherapy of tissues harboring cancer. Photomed Laser Surg 30:551–558

    Article  Google Scholar 

  • Neven E, De Schutter TM, De Broe ME, D’Haese PC (2011) Cell biological and physicochemical aspects of arterial calcification. Kidney Int 79:1166–1177

    Article  CAS  Google Scholar 

  • Okamoto S, Pouladi MA, Talantova M, Yao D, Xia P, Ehrnhoefer DE, Zaidi R, Clemente A, Kaul M, Graham RK, Zhang D, Vincent Chen HS, Tong G, Hayden MR, Lipton SA (2009) Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin. Nat Med 15:1407–1413

    Article  CAS  Google Scholar 

  • Olton DY, Close JM, Sfeir CS, Kumta PN (2011) Intracellular trafficking pathways involved in the gene transfer of nano-structured calcium phosphate-DNA particles. Biomaterials 32:7662–7670

    Article  CAS  Google Scholar 

  • Price PA, Williamson MK, Nguyen TM, Than TN (2004) Serum levels of the fetuin–mineral complex correlate with artery calcification in the rat. J Biol Chem 279:1594–1600

    Article  CAS  Google Scholar 

  • Proudfoot D, Skepper JN, Hegyi L, Bennett MR, Shanahan CM, Weissberg PL (2000) Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies. Circ Res 87:1055–1062

    Article  CAS  Google Scholar 

  • Raoult D, Drancourt M, Azza S, Nappez C, Guieu R, Rolain JM, Fourquet P, Campagna B, La Scola B, Mege JL, Mansuelle P, Lechevalier E, Berland Y, Gorvel JP, Renesto P (2008) Nanobacteria are mineralo fetuin complexes. PLoS Pathog 4:e41

    Article  Google Scholar 

  • Reynolds JL, Joannides AJ, Skepper JN, McNair R, Schurgers LJ, Proudfoot D, Jahnen-Dechent W, Weissberg PL, Shanahan CM (2004) Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. J Am Soc Nephrol 15:2857–2867

    Article  CAS  Google Scholar 

  • Samuel SP, Jain N, O’Dowd F, Paul T, Kashanin D, Gerard VA, Gun’ko YK, Prina-Mello A, Volkov Y (2012) Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow. Int J Nanomed 7:2943–2956

    CAS  Google Scholar 

  • Schlieper G, Krüger T, Heiss A, Jahnen-Dechent W (2011) A red herring in vascular calcification: ‘nanobacteria’ are protein–mineral complexes involved in biomineralization. Nephrol Dial Transplant 26:3436–3439

    Article  CAS  Google Scholar 

  • Sergent JA, Paget V, Chevillard S (2012) Toxicity and genotoxicity of nano-SiO2 on human epithelial intestinal HT-29 cell line. Ann Occup Hyg 56:622–630

    CAS  Google Scholar 

  • Shanahan CM (2005) Mechanisms of vascular calcification in renal disease. Clin Nephrol 63:146–157

    CAS  Google Scholar 

  • Shapero K, Fenaroli F, Lynch I, Cottell DC, Salvati A, Dawson KA (2011) Time and space resolved uptake study of silica nanoparticles by human cells. Mol Biosyst 7:371–378

    Article  CAS  Google Scholar 

  • Shi J, Karlsson HL, Johansson K, Gogvadze V, Xiao L, Li J, Burks T, Garcia-Bennett A, Uheida A, Muhammed M, Mathur S, Morgenstern R, Kagan VE, Fadeel B (2012) Microsomal glutathione transferase 1 protects against toxicity induced by silica nanoparticles but not by zinc oxide nanoparticles. ACS Nano 6:1925–1938

    Article  CAS  Google Scholar 

  • Sommer AP, Miyake N, Wickramasinghe NC, Narlikar JV, Al-Mufti S (2004) Functions and possible provenance of primordial proteins. J Proteome Res 3:1296–1299

    Article  CAS  Google Scholar 

  • Sommer AP, Zhu D, Scharnweber T, Fecht HJ (2010) On the social behaviour of cells. J Bionic Eng 7:1–5

    Article  Google Scholar 

  • Sommer AP, Zhu D, Mester AR, Försterling HD (2011) Pulsed laser light forces cancer cells to absorb anticancer drugs—the role of water in nanomedicine. Artif Cells Blood Substit Immobil Biotechnol 39:169–173

    Article  CAS  Google Scholar 

  • Tulunay Kaya C, Sinan Ertas F, Hasan T, Candemir B, Ozdol C, Arikan Akan O, Kocum T, Dincer I, Sahin M, Atmaca Y, Conkbayr C, Erol C (2011) Anticalcifying nanoparticle antibody titer is an independent risk factor for coronary artery calcification. Coron Artery Dis 22:394–400

    Article  Google Scholar 

  • Wu CY, Martel J, Young D, Young JD (2009) Fetuin-A/albumin–mineral complexes resembling serum calcium granules and putative nanobacteria: demonstration of a dual inhibition-seeding concept. PLoS ONE 4:e8058

    Article  Google Scholar 

  • Young JD, Martel J (2010) The rise and fall of nanobacteria. Sci Am 302:52–59

    Article  CAS  Google Scholar 

  • Young JD, Martel J, Young D, Young A, Hung CM, Young L, Chao YJ, Young J, Wu CY (2009a) Characterization of granulations of calcium and apatite in serum as pleomorphic mineralo-protein complexes and as precursors of putative nanobacteria. PLoS ONE 4:e5421

    Article  Google Scholar 

  • Young JD, Martel J, Young L, Wu CY, Young A, Young D (2009b) Putative nanobacteria represent physiological remnants and culture by-products of normal calcium homeostasis. PLoS ONE 4:e4417

    Article  Google Scholar 

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Acknowledgments

The authors thank Takashi Suematsu, Central Electron Microscope Laboratory, Nagasaki University Graduate School of Biomedical Sciences, for performing the SEM analysis. In addition, the authors thank Masahiro Nakashima, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, for tissue preparations and their examination.

Conflict of interest

The authors report no conflicts of interest in this work.

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Authors and Affiliations

  1. Institute of Micro and Nanomaterials, University of Ulm, 89081, Ulm, Germany

    Andrei P. Sommer

  2. Department of Macroscopic Anatomy, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan

    Toshiyuki Tsurumoto

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  1. Andrei P. Sommer
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  2. Toshiyuki Tsurumoto
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Correspondence to Andrei P. Sommer.

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Sommer, A.P., Tsurumoto, T. Vascular cemeteries formed by biological nanoparticles. J Nanopart Res 15, 1506 (2013). https://doi.org/10.1007/s11051-013-1506-8

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  • DOI: https://doi.org/10.1007/s11051-013-1506-8

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