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Nephrol Dial Transplant. 2015 Dec;30(12):1995-2005. doi: 10.1093/ndt/gfv265. Epub 2015 Jul 16.

Heterogeneous susceptibility for uraemic media calcification and concomitant inflammation within the arterial tree.

Author information

1
Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Graz, Austria.
2
Center of Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
3
Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
4
Institute of Chemistry-Analytical Chemistry, Karl-Franzens University of Graz, Graz, Austria.
5
Center for Medical Research, Core Facility Molecular Biology, Medical University of Graz, Graz, Austria.
6
Department of Radiology, Medical University of Graz, Graz, Austria.
7
Renal Division, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München-Innenstadt, Munich, Germany.
8
Center for Biomedicine, European Academy of Bolzano/Bozen, Bozen, Italy.
9
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.

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.

CONCLUSION:

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.

KEYWORDS:

ESRD; atherosclerosis; coronary calcification; inflammation; vascular calcification

PMID:
26185049
PMCID:
PMC4656037
DOI:
10.1093/ndt/gfv265
[Indexed for MEDLINE]
Free PMC Article

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