Key result
Imidapril attenuated elastase-induced abdominal aortic aneurysm progression and aortic expansion in AT1 receptor-knockout mice, likely through direct inhibition of MMP-9 activity.
Why the study?
Does imidapril reduce aortic expansion and MMP-9 activity in mice with elastase-induced abdominal aortic aneurysm?
Does imidapril reduce aortic expansion and MMP-9 activity in mice with elastase-induced abdominal aortic aneurysm?
Imidapril attenuates abdominal aortic aneurysm progression in mice via direct inhibition of MMP-9, independent of the AT1 receptor pathway.
Imidapril's MMP-9 inhibition in mouse AAA merits targeted trials; leaves open translation to human therapy.
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.
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Takai et al. (2013) studied Abdominal aortic aneurysm (n=42). Imidapril vs. Placebo (0.1% carboxymethyl cellulose) was evaluated on Aortic diameter expansion and MMP-9 activity. Imidapril attenuated elastase-induced abdominal aortic aneurysm progression and aortic expansion in AT1 receptor-knockout mice, likely through direct inhibition of MMP-9 activity.
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