Contribution of Bone Morphogenetic Protein-2 to Aortic Valve Calcification in Aged Rat
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概要
- 論文の詳細を見る
Although aging is well established as an important risk factor for aortic stenosis, the mechanism of age-related aortic valve calcification is yet unknown. Here, we investigated this mechanism in tissue and cellular levels using middle-aged rats. Aortic valve specimens were obtained by dissecting from 9-week-old (young) and 30-week-old (aged) male Wistar rats. In the aged rats, the main risk factors for aortic stenosis in plasma were still in the normal range; however, their number of calcified specimens was significantly increased in comparison with the young rats. Aortic valve interstitial cells (AVICs) obtained from explants of aortic valve specimens were cultured for 14 days after reaching confluence. Spontaneous calcification, the expressions of calcigenic genes, that is, BMP-2, alkaline phosphatase (ALP), and osterix (osteogenic transcription factor) and ALP enzyme activity in AVICs from aged rats were enhanced in comparison with those from young rats. However, neither typical calcification inducing reagents (dexamethasone, β-glycerophosphate, and high concentration of phosphate) nor tumor necrosis factor-α (an inflammatory cytokine) accelerated the spontaneous calcification of AVICs from aged rats. These results suggest that aortic valve calcification progresses with age partly through an activation of the BMP-2 pathway.
著者
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Motomura Shigeru
Department of Pharmacology, Hirosaki University Graduate School of Medicine
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Okumura Ken
Department of Cardiology Respiratory Medicine and Nephrology, Hirosaki University Graduate School of
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KANEMARU Kouta
Department of Pharmacology, Hirosaki University Graduate School of Medicine
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SEYA Kazuhiko
Department of Pharmacology, Hirosaki University Graduate School of Medicine
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FURUKAWA Ken-Ichi
Department of Pharmacology, Hirosaki University Graduate School of Medicine
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Okumura Ken
Department Of Cardiology Hirosaki University Graduate School Of Medicine
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Fukuda Ikuo
Department of Thoracic and Cardiovascular Surgery, Hirosaki University Graduate School of Medicine
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Yu Zaiqiang
Department of Thoracic and Cardiovascular Surgery, Hirosaki University Graduate School of Medicine,
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Daitoku Kazuyuki
Department of Thoracic and Cardiovascular Surgery, Hirosaki University Graduate School of Medicine,
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Akemoto Yui
Department of Pharmacology, Hirosaki University Graduate School of Medicine, Japan
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Shibuya Hiroyuki
Department of Pharmacology, Hirosaki University Graduate School of Medicine, Japan
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Fukuda Ikuo
Department Of Cardiovascular Surgery Hirosaki University School Of Medicine
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Seya Kazuhiko
Department Of Pharmacology Hirosaki University Graduate School Of Medicine
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Seya K
The Second Department Of Surgery Tohoku University School Of Medicine
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Kanemaru Kouta
Department Of Pharmacology Hirosaki University Graduate School Of Medicine
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Motomura Shigeru
Department Of Pharmacology Hirosaki University
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Furukawa Ken-ichi
Department Of Molecular Physiology National Cardiovascular Center Research Institute
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Daitoku Kazuyuki
Department Of Cardiovascular Surgery Hirosaki University School Of Medicine
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Shibuya Hiroyuki
Department Of Pathology Niigata City General Hospital
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Akemoto Yui
Department Of Pharmacalogy Respiratory Medicine And Nephrology Hirosaki University Graduate School O
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Yu Zaiqiang
Department Of Thoracic And Cardiovascular Surgery Respiratory Medicine And Nephrology Hirosaki Unive
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Kanemaru Kouta
Department Of Pharmacalogy Respiratory Medicine And Nephrology Hirosaki University Graduate School O
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