Microcalcifications in atherosclerotic lesion of apolipoprotein E-deficient mouse.
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.
Debernardi
Nicola
N
Department of Applied Physics, Eindhoven University of Technology, Eindhoven, The Netherlands.
Roijers
Ruben B
RB
Krams
Rob
R
de Crom
Rini
R
Mutsaers
Peter H A
PH
van der Vusse
Ger J
GJ
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology*; D002114:Calcinosis / Q000235:genetics / Q000473:pathology*; D002118:Calcium / Q000032:analysis; D002339:Carotid Arteries / Q000737:chemistry / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D010758:Phosphorus / Q000032:analysis; D013314:Stress, Mechanical; D017539:Tunica Intima / Q000473:pathology; D015032:Zinc / Q000032:analysis
D001057:Apolipoproteins E; D010758:Phosphorus; D015032:Zinc; D002118:Calcium
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