Drug efficacy against aortic dissection
(井澤)石澤, 有紀 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
今西, 正樹 Tokushima University 徳島大学 教育研究者総覧
座間味, 義人 Tokushima University KAKEN研究者をさがす
Toya, Hiroki Tokushima University
Nagao, Tomoko Tokushima University
Morishita, Marin Okayama University
常山, 幸一 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
堀ノ内, 裕也 Tokushima University
木平, 孝高 Fukuyama University KAKEN研究者をさがす
武智, 研志 Tokushima University
池田, 康将 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
土屋, 浩一郎 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
吉栖, 正典 Nara Medical University
玉置, 俊晃 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
石澤, 啓介 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
lysyl oxidase inhibitor
nitric oxide synthase inhibitor
the Japanese Adverse Drug Event Report Database
Objective: Aortic dissection is a life-threatening disease. At present, the only therapeutic strategies available are surgery and antihypertensive drugs. Moreover, the molecular mechanisms underlying the onset of aortic dissection are still unclear. We established a novel aortic dissection model in mice using pharmacologically induced endothelial dysfunction. We then used the Japanese Adverse Drug Event Report database to investigate the role of pitavastatin in preventing the onset of aortic dissection.
Methods and results: To induce endothelial dysfunction, Nω-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, was administered to C57BL/6 mice. Three weeks later, angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, were administered with osmotic mini-pumps. False lumen formation was used as the pathological determinant of aortic dissection. The incidences of aortic dissection and death from aneurysmal rupture were significantly higher in the Nω-nitro-L-arginine methyl ester, Ang II, and BAPN (LAB) group than they were in the Ang II and BAPN (AB) group.
Pitavastatin was administered orally to LAB mice. It significantly lowered the incidences of dissection and rupture. It also decreased inflammation and medial degradation, both of which were exacerbated in the LAB group. The Japanese Adverse Drug Event Report database
analysis indicated that there were 113 cases of aortic dissection out of 95 090 patients (0.12%) not receiving statins but only six cases out of 16 668 patients receiving statins (0.04%) (odds ratio: 0.30; P=0.0043).
Conclusion: Our results suggest that endothelial dysfunction is associated with the onset of aortic dissection and pitavastatin can help prevent this condition.
Journal of Hypertension
Wolters Kluwer Health
© 2018 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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