Lack of Endothelial Nitric Oxide Synthase Accelerates Ectopic Calcification in Uremic Mice Fed an Adenine and High Phosphorus Diet
| Autor: | Sadayoshi Ito, Mariko Miyazaki, Hiroshi Sato, Akiyo Sekimoto, Emiko Sato, Yuji Oe, Nobuyuki Takahashi, Shohei Mitsui, Naoko Shibata, Kiyomi Kisu |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Nitric Oxide Synthase Type III Exacerbation 030204 cardiovascular system & hematology medicine.disease_cause Pathology and Forensic Medicine Mice 03 medical and health sciences chemistry.chemical_compound Ectopic calcification 0302 clinical medicine Enos medicine.artery Internal medicine medicine Animals Renal Insufficiency Chronic Aorta Uremia Kidney biology business.industry Adenine Calcinosis Phosphorus biology.organism_classification medicine.disease Diet Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Mice Inbred DBA business Nicotinamide adenine dinucleotide phosphate Oxidative stress Kidney disease |
| Zdroj: | The American Journal of Pathology. 191:283-293 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2020.10.012 |
| Popis: | Ectopic calcification is a risk of cardiovascular disease in chronic kidney disease (CKD) patients, and impaired endothelial nitric oxide synthase (eNOS) is involved in the CKD complications. However, whether eNOS dysfunction is a cause of ectopic calcification in CKD remains to be elucidated. To address this issue, we investigated the role of eNOS in ectopic calcification in mice with renal injury caused by an adenine and high-phosphorus (Ade + HP) diet. DBA/2J mice, a calcification-sensitive strain, were fed Ade + HP for 3 weeks. Expression levels of eNOS-related genes were reduced significantly in their calcified aorta. C57BL/6J is a calcification-resistant strain, and wild-type mice showed mild calcified lesions in the aorta and kidney when given an Ade + HP diet for 4 weeks. In contrast, a lack of eNOS led to the development of severe aortic calcification accompanied by an increase in runt-related transcription factor 2, an osteochondrogenic marker. Increased renal calcium deposition and the tubular injury score were remarkable in mice lacking eNOS-fed Ade + HP. Exacerbation of ectopic calcification by a lack of eNOS is associated with increased oxidative stress markers such as nicotinamide adenine dinucleotide phosphate oxidases. In conclusion, eNOS is critically important in preventing ectopic calcification. Therefore, the maintenance of eNOS is useful to reduce cardiovascular disease events and to improve prognosis in CKD patients. |
| Databáze: | OpenAIRE |
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