Medial calcification (whitlockite) in the aorta

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      Calcified deposits in the tunica media of the human aorta have been studied in 128 cases by light microscopy and by electron microscopy and analytical methods in selected samples. Although dissolved and not visible in routine histology with alum hematoxylin stains, such calcification can be clearly seen after methylene blue staining in the form of unstained refractile particles of 1–2 μm size. These are found between the elastic laminae chiefly in the inner two-thirds of the media and appear at about age 20. By X-ray diffraction supported by energy dispersive X-ray analysis, they have been identified as whitlockite (Ca,Mg)3(PO4)2. Statistical analysis shows a significant increase in numbers with age and significant differences in severity related to county of origin but no differences between sexes or races and no correlation with deaths related to cardiovascular diseases. Among various substructures of the aortic wall, no unique crystal precursor was identified. Possible etiologic factors and clinicopathologic significance are considered.


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        • Klotz O.
        Studies upon calcareous degeneration. I The process of pathological calcification.
        J. Exp. Med. 1905; 7: 633
        • Blumenthal H.T.
        • Lansing A.I.
        • Wheeler P.A.
        Calcification of the media of the human aorta and its relation to intimal arteriosclerosis, ageing and disease.
        Am. J. Pathol. 1944; 20: 665
        • Franca L.C.M.
        • Foraker A.G.
        Elastic laminae and ground substance of arteriosclerosic aortas. An interferometric approach.
        Arch. Pathol. 1961; 71: 408
        • Bertelsen S.
        The role of ground substance, collagen, and elastic fibers in the genesis of atherosclerosis.
        in: Sandier M. Bourne G.H. Atherosclerosis and Its Origin. Academic Press, New York, London1963 (Chap. 4)
        • Yu S.Y.
        • Blumenthal H.T.
        The calcification of elastic fibers. I Biochemical studies.
        J. Gerontol. 1963; 18: 119
        • Blankenhorn D.H.
        Relation of diffuse aortic calcification to atherosclerotic calcification.
        J. Atheroscler. Res. 1964; 4: 313
        • Gardner M.B.
        • Blankenhorn D.H.
        Aortic medial calcification. An ultrastructural study.
        Arch. Pathol. 1968; 85: 397
        • Paegle R.D.
        Ultrastructure of calcium deposits in arteriosclerosic human aortas.
        J. Ultrastruct. Res. 1969; 26: 412
        • Kim K.M.
        • Trump B.F.
        Electron microscopic study on calcification of human aorta.
        Circulation. 1972; 46 (Suppl.): 11-176
        • Burger M.
        Z. Neurol. Psychol. 1939; 167 (quoted by Fleckenstein [23]): 233
        • Lansing A.I.
        • Alex M.
        • Rosenthal T.B.
        Calcium and elastin in human arteriosclerosis.
        J. Gerontol. 1950; 5: 112
        • Weissmann G.
        • Weissmann S.
        X-Ray diffraction studies of human aortic elastin residues.
        J. Clin. Invest. 1960; 39: 1657
        • Geever E.F.
        • McCann H.G.
        • McClure F.J.
        • Lee W.A.
        • Schiffmann E.
        Fluoridated water, skeletal structure, and chemistry.
        HSMHA Health Rep. 1971; 86: 820
        • Conn H.J.
        The history of staining. Logwood dyes.
        Stain. Technol. 1929; 4: 37
        • Kim K.M.
        Calcification of matrix vesicles in human aortic valve and aortic media.
        in: 3rd Edn. Fed. Proc.35. 1976: 156
        • Yu S.Y.
        • Blumenthal H.T.
        The calcification of elastic fibers. II Ultramicroscopic characteristics.
        J. Gerontol. 1963; 18: 127
        • Serafini-Fracassini A.
        Electron microscope and X-Ray crystal analysis of the calcified elastic tissue.
        J. Atheroscler. Res. 1963; 3: 178
        • Yu S.Y.
        • Blumenthal H.T.
        The calcification of elastic fiber. III Various crystalline structures of apatite in human aortae.
        Lab. Invest. 1963; 12: 1154
        • Martin G.R.
        • Schiffmann E.
        • Bladen H.A.
        • Nylen M.
        Chemical and morphologic studies on the in vitro calcification of aorta.
        J. Cell. Biol. 1963; 16: 243
        • Frondel C.
        Whitlockite: A new calcium phosphate, Ca3(PO4)2.
        Am. Mineral. 1941; 26: 145
        • LeGeros R.Z.
        Calcium phosphates in oral biology and medicine.
        in: 3rd Edn. Monographs in Oral Science. Vol: 15. Karger, Basel1991
        • Eisenstein R.
        • Zeruolis L.
        Vitamin D-induced aortic calcification. An electron microscopic study.
        Arch. Pathol. 1964; 77: 27
        • Fleckenstein A.
        Calcium Antagonism in Heart and Smooth Muscle. Experimental Facts and Therapeutic Prospects.
        John Wiley & Sons, New York1983
        • Fleckenstein A.
        • Frey M.
        • Zorn J.
        • Fleckenstein-Grün G.
        The role of calcium in the pathogenesis of experimental arteriosclerosis.
        Trends Pharmacol. Sci. 1987; 8: 496
        • Susheela A.K.
        • Kharb P.
        Aortic calcification in chronic fluoride poisoning: biochemical and electronmicroscopic evidence.
        Exp. Mol. Pathol. 1990; 53: 72
        • Juul S.
        • Ledbetter D.
        • Wight T.N.
        • Woodrum D.
        New insights into idiopathic infantile arterial calcinosis. Three patient reports.
        Am. J. Dis. Child. 1900; 144: 229
        • Romeo R.
        • Augustyn J.M.
        • Mandel G.
        Isolation and characterization of human apatite-inducing aortic proteolipid.
        Exp. Mol. Pathol. 1989; 51: 149
        • Dmitrovsky E.
        • Boskey A.L.
        Calcium-acidic phospholipid-phosphate complexes in human atherosclerotic aortas.
        Calcif. Tissue Int. 1985; 37: 121
        • Boyan B.D.
        • Schwartz Z.
        • Swain L.D.
        • Khare A.
        Role of lipids in calcification of cartilage.
        Anat. Rec. 1989; 224: 211
        • Anderson H.C.
        Mechanisms of pathologic calcification.
        Rheum. Dis. Clin. North Am. 1988; 14: 303
        • Genge B.R.
        • Wu L.N.Y.
        • Wuthier R.E.
        Identification of phospholipid dependent calcium-binding proteins as constituents of matrix vesicles.
        J. Biol. Chem. 1989; 264: 10917
        • Boskey A.L.
        • Bullough P.G.
        • Vigorita V.
        • DiCarlo E.
        Calcium-acidic phospholipid-phosphate complexes in human hydroxyapatite-containing pathologic deposits.
        Am. J. Pathol. 1988; 133: 22
        • Sandberg L.B.
        • Soskel N.T.
        • Leslie J.G.
        Elastin structure, biosynthesis, and relation to disease states.
        N. Engl. J. Med. 1981; 304: 566
        • Ghadially F.N.
        Ultrastructural Pathology of the Cell and Matrix. A Text and Atlas of Physiological and Pathological Alterations in the Fine Structure of Cellular and Extracellular Components.
        3rd Edn. Butterworths, London, Boston1988
        • Rowles S.L.
        The precipitation of whitlockite from aqueous solutions.
        Bull. Soc. Chim. Franc. 1968; : 1797
        • Tomazic B.B.
        • Etz E.S.
        • Brown W.E.
        Nature and properties of cardiovascular deposits.
        Scanning Microsc. 1987; 1: 95