Significance of Matrix Metalloproteinase-9 Inhibition by Imidapril for Prevention of Abdominal Aortic Aneurysms in Angiotensin II Type 1 Receptor–Knockout Mice

Journal of Pharmacological Sciences

Zhong-Lian Li²  Shinji Takai³  Daisuke Yamamoto¹  Mizuo Miyazaki³  Denan Jin³  Yoshinori Otsuki² 

[1] Biomedical Computation Center, Osaka Medical College, Japan;Department of Anatomy and Cell Biology, Osaka Medical College, Japan;Department of Pharmacology, Osaka Medical College, Japan

关键词: aneurysm;    angiotensin II;    angiotensin-converting enzyme;    inhibitor;    matrix metalloproteinase-9;   

DOI  :  10.1254/jphs.13040FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(45)Cited-By(2)To clarify the matrix metalloproteinase (MMP)-9 inhibitory effect of an angiotensin-converting enzyme (ACE) inhibitor in vivo, we evaluated the effect of an ACE inhibitor against elastase-induced abdominal aortic aneurysm (AAA) progression in mice. Molecular models showed that imidapril bound directly to the mouse MMP-9 active center. An active form of imidapril, imidaprilat, dose-dependently inhibited MMP-9 activity in the extract from elastase-induced AAA in wild-type mice. Imidapril (10 mg/kg per day) was administered to wild-type or angiotensin II type 1 (AT1) receptor knockout mice. Blood pressure was significantly lower in AT1 receptor–knockout mice than in wild-type mice, but imidapril did not affect blood pressure in AT1 receptor–knockout mice. The aortic diameter was significantly expanded after elastase application, but the expansion was significantly lower in AT1 receptor–knockout mice than in wild-type mice. In AT1 receptor–knockout mice, the aortic expansion was further attenuated by imidapril. MMP-9 activity in aorta was significantly augmented after elastase application. The MMP-9 activity was significantly lower in AT1 receptor–knockout mice than in wild-type mice, and it was further attenuated by imidapril. In conclusion, MMP-9 inhibition by imidapril might contribute to the attenuation of AAA progression in AT1 receptor–knockout mice.

【 授权许可】

Unknown