Evidence is accumulating that calcium-rich microdeposits in the vascular wall might play a crucial role in the onset and progression of atherosclerosis. Here we investigated an atherosclerotic lesion of the carotid artery in an established murine model, i.e. the apolipoprotein E-deficient (APOE-/-) mouse to identify (i) the presence of microcalcifications, if any, (ii) the elemental composition of microcalcifications with special reference to calcium/phosphorus mass ratio and (iii) co-localization of increased concentrations of iron and zinc with microcalcifications. Atherosclerosis was induced by a flow-divider placed around the carotid artery resulting in low and high shear-stress regions. Element composition was assessed with a proton microprobe. Microcalcifications, predominantly present in the thickened intima of the low shear-stress region, were surrounded by areas with normal calcium levels, indicating that calcium-precipitation is a local event. The diameter of intimal microcalcifications varied from 6 to 70 μm. Calcium/phosphorus ratios of microcalcifications varied from 0.3 to 4.8, mainly corresponding to the ratio of amorphous calcium-phosphate. Increased iron and zinc concentrations commonly co-localized with microcalcifications. Our findings indicate that the atherosclerotic process in the murine carotid artery is associated with locally accumulated calcium, iron and zinc. The calcium-rich deposits resemble amorphous calcium phosphate rather than pure hydroxyapatite. We propose that the APOE-/- mouse, in which atherosclerosis was evoked by a flow-divider, offers a useful model to investigate the pathophysiological significance of accumulation of elements such as calcium, iron and zinc.

Additional Metadata
Keywords Atherosclerosis, Iron, Microcalcification, Proton microprobe, Zinc
Persistent URL dx.doi.org/10.1111/j.1365-2613.2010.00729.x, hdl.handle.net/1765/21903
Citation
Debernardi, N, Roijers, R.B, Krams, R, de Crom, M.P.G, Mutsaers, P.H, & van der Vusse, G.J. (2010). Microcalcifications in atherosclerotic lesion of apolipoprotein E-deficient mouse. International Journal of Experimental Pathology: mechanisms and models of disease, 91(6), 485–494. doi:10.1111/j.1365-2613.2010.00729.x