Journal
AMERICAN JOURNAL OF NEPHROLOGY
Volume 33, Issue 3, Pages 250-259Publisher
KARGER
DOI: 10.1159/000324693
Keywords
Chronic kidney disease; Blood urea nitrogen; Receptor for advanced glycation endproducts
Categories
Funding
- National Institute of Health [K08 HL090917-02, K08HL098565-01]
- GlaxoSmithKline Research & Education Foundation for Cardiovascular Diseases
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K08HL090917, K08HL098565] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Background: The proinflammatory cytokine S100A12 (also known as EN-RAGE) is associated with cardiovascular morbidity and mortality in hemodialysis patients. In the current study, we tested the hypothesis that S100A12 expressed in vascular smooth muscle in nonatherosclerosis-prone C57BL/6J mice on normal rodent chow diet, but exposed to the metabolic changes of chronic kidney disease (CKD), would develop vascular disease resembling that observed in patients with CKD. Methods: CKD was induced in S100A12 transgenic mice and wild-type littermate mice not expressing human S100A12 by surgical ligation of the ureters. The aorta was analyzed after 7 weeks of elevated BUN (blood urea nitrogen), and cultured aortic smooth muscle cells were studied. Results: We found enhanced vascular medial calcification in S100A12tg mice subjected to CKD. Vascular calcification was mediated, at least in part, by activation of the receptor for S100A12, RAGE (receptor for advanced glycation endproducts), and by enhanced oxidative stress, since inhibition of NADPH-oxidase Nox1 and limited access of S100A12 to RAGE attenuated the calcification and gene expression of osteoblastic genes in cultured vascular smooth muscle cells. Conclusion: S100A12 augments CKD-triggered osteogenesis in murine vasculature, reminiscent of features associated with enhanced vascular calcification in patients with chronic and end-stage kidney disease. Copyright (C) 2011 S. Karger AG, Basel
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available