title: Microcalcifications in atherosclerotic lesion of apolipoprotein E-deficient mouse.
abstract: 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.
authors.affiliation: Department of Applied Physics, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Nicola
authors.initials: N
authors.lastname: Debernardi
authors.forename: Ruben B
authors.initials: RB
authors.lastname: Roijers
authors.forename: Rob
authors.initials: R
authors.lastname: Krams
authors.forename: Rini
authors.initials: R
authors.lastname: de Crom
authors.forename: Peter H A
authors.initials: PH
authors.lastname: Mutsaers
authors.forename: Ger J
authors.initials: GJ
authors.lastname: van der Vusse
mesh_terms: 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
chemical_list: D001057:Apolipoproteins E; D010758:Phosphorus; D015032:Zinc; D002118:Calcium
references.citation: Circulation. 2001 Jul 17;104(3):365-72
references.pmid: 11457759
references.citation: Circulation. 2006 Jun 13;113(23):2744-53
references.pmid: 16754802
references.citation: Atherosclerosis. 1998 Mar;137(1):1-11
references.pmid: 9568731
references.citation: Cell Mol Biol (Noisy-le-grand). 1996 Feb;42(1):17-26
references.pmid: 8833663
references.citation: Anal Chem. 2008 Jan 1;80(1):55-61
references.pmid: 18027908
references.citation: Nature. 2000 Sep 14;407(6801):233-41
references.pmid: 11001066
references.citation: Cardiovasc Res. 1998 Jul;39(1):8-33
references.pmid: 9764187
references.citation: Trends Cardiovasc Med. 2001 Apr-May;11(3-4):103-12
references.pmid: 11685998
references.citation: Nature. 1969 Sep 13;223(5211):1159-60
references.pmid: 5810692
references.citation: Z Kardiol. 2001;90 Suppl 3:116-24
references.pmid: 11374023
references.citation: Physiol Rev. 2004 Oct;84(4):1381-478
references.pmid: 15383655
references.citation: Free Radic Biol Med. 2007 Feb 15;42(4):492-8
references.pmid: 17275681
references.citation: J Clin Invest. 2007 Mar;117(3):616-26
references.pmid: 17304353
references.citation: Z Kardiol. 2001;90 Suppl 3:68-80
references.pmid: 11374037
references.citation: Am J Cardiol. 2001 Jul 19;88(2A):16E-19E
references.pmid: 11473739
references.citation: Cell Mol Biol (Noisy-le-grand). 1996 Feb;42(1):59-67
references.pmid: 8833667
references.citation: Proc Soc Exp Biol Med. 1983 Feb;172(2):173-7
references.pmid: 6828462
references.citation: Invest Radiol. 2007 May;42(5):263-73
references.pmid: 17414521
references.citation: J Biol Chem. 2005 Dec 16;280(50):41521-9
references.pmid: 16216873
references.citation: Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):12-22
references.pmid: 14604830
references.citation: Neurosci Lett. 1998 Jan 16;240(3):123-6
references.pmid: 9502219
references.citation: FASEB J. 2002 Apr;16(6):577-82
references.pmid: 11919160
references.citation: J Inorg Biochem. 2004 Dec;98(12):2032-8
references.pmid: 15541492
references.citation: Am J Cardiol. 2003 Feb 6;91(3A):12A-16A
references.pmid: 12645639
references.citation: Endocrinology. 2003 Jun;144(6):2214-9
references.pmid: 12746277
references.citation: Atherosclerosis. 1980 Oct;37(2):199-210
references.pmid: 7426095
references.citation: Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1420-5
references.pmid: 15845913
references.citation: Vasc Health Risk Manag. 2008;4(2):315-24
references.pmid: 18561507
references.citation: Atherosclerosis. 1998 Jun;138(2):281-8
references.pmid: 9690911
references.citation: Free Radic Biol Med. 2003 Mar 15;34(6):746-52
references.pmid: 12633751
references.citation: Herz. 2001 Jun;26(4):245-51
references.pmid: 11479936
references.citation: Arterioscler Thromb Vasc Biol. 2004 May;24(5):949-54
references.pmid: 15001454
references.citation: J Clin Invest. 1994 Oct;94(4):1597-604
references.pmid: 7929835
references.citation: Atherosclerosis. 1995 Nov;118(1):9-21
references.pmid: 8579636
references.citation: Trends Cardiovasc Med. 1998 Jul;8(5):199-206
references.pmid: 14987565
references.citation: Circ Res. 2008 Jun 20;102(12):1529-38
references.pmid: 18497329