A red herring in vascular calcification: 'nanobacteria' are protein-mineral complexes involved in biomineralization

Abstract

Biomineralization at pathological extraosseous sites (i.e. vasculature and soft tissues) is associated with increased morbidity and mortality. So-called 'nanobacteria' have been described as pathogenic agents causing many diseases including calcification. Initially, their appearance, and having a content consisting of nucleic acids plus proteins and properties of growing structures, suggested that they were living organisms. However, it could be demonstrated that the so-called nanobacteria were in fact mineralizing nanoparticles that contain mineral and non-mineral compounds, that these particles bind to charged molecules and that supersaturation enables in vitro growth of these nanoparticles. Recent data indicate that nanoparticles consisting of protein-mineral complexes can be seen both in vitro and in vivo as precursors of matrix calcification.

Fig. 1.

Transmission electron micrograph of so-called ‘nanobacteria’ after a 3-month culture period (bar = 200 nm). Photograph taken with permission from [6] (copyright 1998 National Academy of Sciences, USA).

Fig. 2.

Illustration of a CPP, calciprotein monomer (modified after [18, 19]) and a low-density lipoprotein (LDL) particle. The LDL particle is ∼22 nm in diameter and contains many esterified cholesterol molecules in the hydrophobic core, cholesterol, phospholipids and a few apolipoprotein B-100 molecules in the hydrophilic coat (modified after [20]).

Fig. 3.

Electron microscopic picture of synthetic CCPs [22]. The CCPs initially have a diameter of 30–150 nm (2 h, 37°C) and are amorphous as shown by diffraction analysis. Nextly, the CPPs are transformed, dependent on temperature, mineral ion supersaturation and fetuin-A concentration, into larger and crystalline mineral particles [23]. These particles are still soluble until ∼24 h at 37°C. Similar particles have been detected in ascites of patients with sclerosing calcifying peritonitis [24]. Scale bars represents 100 nm. This research was originally published in [22] © the American Society for Biochemistry and Molecular Biology.