Biomaterial Database

Ultrastructural analysis of vascular calcifications in uremia. 2010

Georg Schlieper, and Anke Aretz, and Steven C Verberckmoes, and Thilo Krüger, and Geert J Behets, and Reza Ghadimi, and Thomas E Weirich, and Dorothea Rohrmann, and Stephan Langer, and Jan H Tordoir, and Kerstin Amann, and Ralf Westenfeld, and Vincent M Brandenburg, and Patrick C D'Haese, and Joachim Mayer, and Markus Ketteler, and Marc D McKee, and Jürgen Floege

Department of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. gschlieper@ukaachen.de

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.

UI	MeSH Term	Description	Entries
D007676	Kidney Failure, Chronic	The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.	ESRD,End-Stage Renal Disease,Renal Disease, End-Stage,Renal Failure, Chronic,Renal Failure, End-Stage,Chronic Kidney Failure,End-Stage Kidney Disease,Chronic Renal Failure,Disease, End-Stage Kidney,Disease, End-Stage Renal,End Stage Kidney Disease,End Stage Renal Disease,End-Stage Renal Failure,Kidney Disease, End-Stage,Renal Disease, End Stage,Renal Failure, End Stage
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D002114	Calcinosis	Pathologic deposition of calcium salts in tissues.	Calcification, Pathologic,Calcinosis, Tumoral,Microcalcification,Microcalcinosis,Pathologic Calcification,Calcinoses,Calcinoses, Tumoral,Microcalcifications,Microcalcinoses,Tumoral Calcinoses,Tumoral Calcinosis
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014511	Uremia	A clinical syndrome associated with the retention of renal waste products or uremic toxins in the blood. It is usually the result of RENAL INSUFFICIENCY. Most uremic toxins are end products of protein or nitrogen CATABOLISM, such as UREA or CREATININE. Severe uremia can lead to multiple organ dysfunctions with a constellation of symptoms.	Uremias
D014652	Vascular Diseases	Pathological processes involving any of the BLOOD VESSELS in the cardiac or peripheral circulation. They include diseases of ARTERIES; VEINS; and rest of the vasculature system in the body.	Disease, Vascular,Diseases, Vascular,Vascular Disease
D017540	Tunica Media	The middle layer of blood vessel walls, composed principally of thin, cylindrical, smooth muscle cells and elastic tissue. It accounts for the bulk of the wall of most arteries. The smooth muscle cells are arranged in circular layers around the vessel, and the thickness of the coat varies with the size of the vessel.	Vascular Media,Arterial Media,Venous Media,Arterial Medias,Media, Arterial,Media, Vascular,Media, Venous,Medias, Arterial,Medias, Vascular,Medias, Venous,Vascular Medias,Venous Medias