| アブストラクト | 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, Nomega-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, was administered to C57BL/6 mice. Three weeks later, angiotensin II (Ang II) and beta-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 Nomega-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. |
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| ジャーナル名 | Journal of hypertension |
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| 投稿日 | 2018/10/12 |
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| 投稿者 | Izawa-Ishizawa, Yuki; Imanishi, Masaki; Zamami, Yoshito; Toya, Hiroki; Nagao, Tomoko; Morishita, Marin; Tsuneyama, Koichi; Horinouchi, Yuya; Kihira, Yoshitaka; Takechi, Kenshi; Ikeda, Yasumasa; Tsuchiya, Koichiro; Yoshizumi, Masanori; Tamaki, Toshiaki; Ishizawa, Keisuke |
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| 組織名 | Department of Pharmacology, Tokushima University, Graduate School of Biomedical;Sciences.;Department of Pharmacy, Tokushima University Hospital.;Department of Clinical Pharmacology and Therapeutics.;Department of Medical Pharmacology, Tokushima University, Graduate School of;Biomedical Sciences.;Department of Emergency Pharmaceutical Sciences, Okayama University Graduate;School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama.;Department of Pathology and Laboratory Medicine, Tokushima University, Graduate;School of Biomedical Sciences, Tokushima.;Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama.;Clinical Trial Center for Developmental Therapeutics, Tokushima University;Hospital, Tokushima.;Department of Pharmacology, Nara Medical University, Kashihara, Japan. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/30303488/ |
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