title: Heterogeneous susceptibility for uraemic media calcification and concomitant inflammation within the arterial tree.
abstract: BACKGROUND
  End-stage renal disease (ESRD) is strongly associated with arterial calcification of the tunica media, decreased vascular compliance and sudden cardiac death. Here, we analysed the distribution pattern of uraemic media calcification and concomitant inflammation in mice and men.
  
  
  METHODS
  Uraemia was induced in DBA/2 mice with high-phosphate diet. Subsequently, we analysed arterial medial calcification using histology, mass spectrometry, and wire myography. Gene expression was quantified using a whole transcriptome array and quantitative PCR. In a cohort of 36 consecutive patients with CKD stage 4-5, we measured the calcium score of the coronary arteries, the ascending thoracic aorta and the infrarenal abdominal aorta using computed tomography scans.
  
  
  RESULTS
  Uraemic DBA/2 mice showed only minor calcifications in thoracic aortas, whereas there was overt media calcification in abdominal aortas. The transcriptional profile and immunohistochemistry revealed induction of Vcam1 expression by vascular smooth muscle cells in uraemic abdominal aortas. Macrophages infiltrated the tunica media of the abdominal aorta. Anti-inflammatory treatment did not improve uraemic media calcification in our animal model. Arterial calcifications in ESRD patients showed a similar distribution pattern in computed tomography scans, with higher calcium scores of the abdominal aorta when compared with the thoracic aorta.
  
  
  CONCLUSIONS
  Taken together, there was a similar heterogeneous pattern of calcification in both mice and humans, where the abdominal aorta was more prone to media calcification when compared with the thoracic aorta. In uraemia, smooth muscle cells of the abdominal aorta showed a phenotypic switch to an inflammatory and osteoblastic phenotype.
authors.affiliation: Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Graz, Austria.
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Kirsch
authors.affiliation: Center of Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
authors.forename: Andrijana
authors.initials: A
authors.lastname: Kirsch
authors.affiliation: Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Graz, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Artinger
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Corinna
authors.initials: C
authors.lastname: Schabhüttl
authors.affiliation: Institute of Chemistry-Analytical Chemistry, Karl-Franzens University of Graz, Graz, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Goessler
authors.affiliation: Center for Medical Research, Core Facility Molecular Biology, Medical University of Graz, Graz, Austria.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Klymiuk
authors.affiliation: Center for Medical Research, Core Facility Molecular Biology, Medical University of Graz, Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Gülly
authors.affiliation: Department of Radiology, Medical University of Graz, Graz, Austria.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Fritz
authors.affiliation: Center of Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
authors.forename: Saša
authors.initials: S
authors.lastname: Frank
authors.affiliation: Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Graz, Austria.
authors.forename: Roxana
authors.initials: R
authors.lastname: Wimmer
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Marianne
authors.initials: M
authors.lastname: Brodmann
authors.affiliation: Renal Division, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München-Innenstadt, Munich, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
authors.affiliation: Center for Biomedicine, European Academy of Bolzano/Bozen, Bozen, Italy.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
authors.affiliation: Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Graz, Austria.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Rosenkranz
authors.affiliation: Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Graz, Austria.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Eller
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria Department of Internal Medicine, Intensive Care Unit, Medical University of Graz, Graz, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Eller
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D014511:Uremia / Q000503:physiopathology*; D061205:Vascular Calcification / Q000503:physiopathology*
chemical_list: D002118:Calcium
keywords: ESRD; atherosclerosis; coronary calcification; inflammation; vascular calcification