W Mohr1, E Görz. 1. Abteilung Pathologie, Universität Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Abstract
OBJECTIVE: Vascular calcification, traditionally regarded as a dystrophic process, has recently been interpreted as a bone-like biologically regulated phenomenon. Because temporal arteries which also contain calcifications are easily available from biopsies of older individuals with suspected giant cell arteritis, we studied the morphogenesis of this calcification in comparison with the development of fetal bone. MATERIAL AND METHODS: Formaldehyde fixed arteries were processed in paraffin sections and investigated by light-, transmission-, and scanning electron microscopy. The atomic composition of the calcifications was estimated by X-ray microanalysis. Fetal bone, also fixed with formaldehyde, was investigated using identical methods. RESULTS: Early calcifications are often present as focal or diffuse granular mediacalcinosis. With increasing age, calcified granules appear in association with the internal elastic membranes and progress to sheet-like calcifications. Ultrastructurally calcospherites, not rarely exhibiting the Liesegang phenomenon, are the hallmark of early calcifications. In advanced sheet-like calcification calcospherites could be detected as components of the calcified lumps. Calcospherites also appear in endochondral calcification, but are absent in calcified osteoid. The ultrastructure of calcospherites in provisional endochondral ossification differs from that in vascular calcification. Instead of corpuscles as with the Liesegang phenomenon, radial clusters of needle-like crystals resembling apatite are present. While calcospherites of the tunica media often contain a high amount of magnesium, calcified sheets as well as bone exhibited in contrast a low magnesium content. CONCLUSIONS: It is concluded that, comparable to granular mediacalcinosis of the aorta, development of calcified arteriosclerotic plaques, and Mönckeberg's disease, calcification of small muscular temporal arteries is also initially a calcospherite-dependent process. It is generally accepted that these calcified corpuscles represent remnants of calcified necrotic or apoptotic cells. In the phase of confluence with the appearance of sheet-like calcification, a low bone-like magnesium content that differs from the high amount in the isolated medial calcospherites was measured. This finding, together with the observation that calcified sheets contain calcospherites, supports the hypothesis that vascular calcification in general is different from bone formation and has to be regarded as a biphasic process initiated by the appearance of calcospherites and followed by a secondary calcifying phase with the formation of bone-like apatite that leads to rock hard lumps of calcified vessels.
OBJECTIVE:Vascular calcification, traditionally regarded as a dystrophic process, has recently been interpreted as a bone-like biologically regulated phenomenon. Because temporal arteries which also contain calcifications are easily available from biopsies of older individuals with suspected giant cell arteritis, we studied the morphogenesis of this calcification in comparison with the development of fetal bone. MATERIAL AND METHODS:Formaldehyde fixed arteries were processed in paraffin sections and investigated by light-, transmission-, and scanning electron microscopy. The atomic composition of the calcifications was estimated by X-ray microanalysis. Fetal bone, also fixed with formaldehyde, was investigated using identical methods. RESULTS: Early calcifications are often present as focal or diffuse granular mediacalcinosis. With increasing age, calcified granules appear in association with the internal elastic membranes and progress to sheet-like calcifications. Ultrastructurally calcospherites, not rarely exhibiting the Liesegang phenomenon, are the hallmark of early calcifications. In advanced sheet-like calcification calcospherites could be detected as components of the calcified lumps. Calcospherites also appear in endochondral calcification, but are absent in calcified osteoid. The ultrastructure of calcospherites in provisional endochondral ossification differs from that in vascular calcification. Instead of corpuscles as with the Liesegang phenomenon, radial clusters of needle-like crystals resembling apatite are present. While calcospherites of the tunica media often contain a high amount of magnesium, calcified sheets as well as bone exhibited in contrast a low magnesium content. CONCLUSIONS: It is concluded that, comparable to granular mediacalcinosis of the aorta, development of calcified arteriosclerotic plaques, and Mönckeberg's disease, calcification of small muscular temporal arteries is also initially a calcospherite-dependent process. It is generally accepted that these calcified corpuscles represent remnants of calcified necrotic or apoptotic cells. In the phase of confluence with the appearance of sheet-like calcification, a low bone-like magnesium content that differs from the high amount in the isolated medial calcospherites was measured. This finding, together with the observation that calcified sheets contain calcospherites, supports the hypothesis that vascular calcification in general is different from bone formation and has to be regarded as a biphasic process initiated by the appearance of calcospherites and followed by a secondary calcifying phase with the formation of bone-like apatite that leads to rock hard lumps of calcified vessels.
Authors: Georg Schlieper; Anke Aretz; Steven C Verberckmoes; Thilo Krüger; Geert J Behets; Reza Ghadimi; Thomas E Weirich; Dorothea Rohrmann; Stephan Langer; Jan H Tordoir; Kerstin Amann; Ralf Westenfeld; Vincent M Brandenburg; Patrick C D'Haese; Joachim Mayer; Markus Ketteler; Marc D McKee; Jürgen Floege Journal: J Am Soc Nephrol Date: 2010-03-04 Impact factor: 10.121
Authors: Sergio Bertazzo; Eileen Gentleman; Kristy L Cloyd; Adrian H Chester; Magdi H Yacoub; Molly M Stevens Journal: Nat Mater Date: 2013-04-21 Impact factor: 43.841