Ultrastructural Analysis of Vascular Calcifications in Uremia

Georg Schlieper*, Anke Aretz, Steven C. Verberckmoes, Thilo Krueger, 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, Juergen Floege

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

117 Citations (Web of Science)

Abstract

Accelerated intimal and medial calcification and sclerosis accompany the increased cardiovascular mortality of dialysis patients, but the pathomechanisms initiating microcalcifications of the media are largely unknown. In this study, we systematically investigated the ultrastructural properties of medial calcifications from patients with uremia. We collected iliac artery segments from 30 dialysis patients before kidney transplantation and studied them by radiography, microcomputed tomography, light microscopy, and transmission electron microscopy including electron energy loss spectrometry, energy dispersive spectroscopy, and electron diffraction. In addition, we performed synchrotron x-ray analyses and immunogold labeling to detect inhibitors of calcification. Von Kossa staining revealed calcification of 53% of the arteries. The diameter of these microcalcifications ranged from 20 to 500 nm, with a core-shell structure consisting of up to three layers (subshells). Many of the calcifications consisted of 2- to 10-nm nanocrystals and showed a hydroxyapatite and whitlockite crystalline structure and mineral phase. Immunogold labeling of calcification foci revealed the calcification inhibitors fetuin-A, osteopontin, and matrix gla protein. These observations suggest that uremic microcalcifications originate from nanocrystals, are chemically diverse, and intimately associate with proteinaceous inhibitors of calcification. Furthermore, considering the core-shell structure of the calcifications, apoptotic bodies or matrix vesicles may serve as a calcification nidus.
Original languageEnglish
Pages (from-to)689-696
JournalJournal of the American Society of Nephrology
Volume21
Issue number4
DOIs
Publication statusPublished - Apr 2010

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