Abstract

BackgroundMedial vascular calcification is a specific complication in chronic kidney disease (CKD) patients although its pathogenesis is poorly understood. The administration of iron (Fe), generally used for the treatment of anemia in CKD patients, induces oxidative stress. Fe loading possibly affects the progress of vascular calcification in uremia. We investigated the effect of Fe on vascular calcification and its mechanism in uremic rats.MethodThirty-two rats were divided into four groups: untreated rats (controls), rats fed a standard diet with Fe administration (Fe group), rats fed an adenine-enriched diet (uremic group), and rats fed an adenine-enriched diet with Fe administration (uremic + Fe group). Iron dextran was administered once a week for 5 weeks intraperitoneally. Morphological alterations and vascular calcification-associated factors in the aortic wall were evaluated.ResultsNo aortic calcification was observed in the control group although uremic rats developed severe vascular calcification. Fe loading suppressed vascular calcification in the uremic groups. Expressions of runt-related transcription factor 2 (Runx2), single-strand (ss)DNA and phosphate transporter (Pit)-1 were increased in the uremic rats compared to the control rats. In the uremic group, Fe administration did not show any effect on ssDNA expression, but reduced Runx2 and Pit-1 expressions.ConclusionFe suppressed the development of vascular calcification through the prevention of Pit-1 and vascular smooth muscle cell osteoblastic transdifferentiation.

Highlights

  • Chronic kidney disease (CKD) is an independent risk factor for the development of cardiovascular disease (CVD) and the increased morbidity and mortality associated with CVD [1]

  • We investigated the effect of Fe on vascular calcification and its mechanism in uremic rats

  • Thirty-two rats were divided into four groups: untreated rats, rats fed a standard diet with Fe administration (Fe group), rats fed an adenine-enriched diet, and rats fed an adenine-enriched diet with Fe administration

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Summary

Introduction

Chronic kidney disease (CKD) is an independent risk factor for the development of cardiovascular disease (CVD) and the increased morbidity and mortality associated with CVD [1]. Medial calcification is a characteristic finding in vascular pathological change in end-stage kidney disease [2]. This pathologic mechanism is caused by a metabolic abnormality of calcium and phosphate [3]. Oxidative stress is generally known as one of the factors affecting endothelial dysfunction and the development of atherosclerosis [5]. Iron (Fe) loading increases oxidative stress and causes endothelial dysfunction. The objective of the present study was to evaluate the effect of Fe on the development of vascular calcification and its mechanism in uremic rats. The administration of iron (Fe), generally used for the treatment of anemia in CKD patients, induces oxidative stress. Morphological alterations and vascular calcification-associated factors in the aortic wall were evaluated

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