ASB17061, a novel chymase inhibitor, prevented the development of angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E-deficient mice

Abstract

Our aim was to examine the effects of ASB17061, an orally active novel chymase inhibitor, on angiotensin II–induced abdominal aortic aneurysm (AAA) in apolipoprotein E–deficient mice. Oral administration of ASB17061 (10 mg/kg) significantly suppressed angiotensin II–induced AAA formation in these mice. The pro-matrix metalloproteinase-9 (pro-MMP-9) level in AAA lesions was significantly suppressed by ASB17061 treatment, indicating that ASB17061 inhibited the accumulation of pro-MMP-9–producing cells in AAA lesions. Mouse mast cell protease 4 (mMCP-4, human chymase ortholog) was injected into BALB/c mice intraperitoneally to examine the ability of mMCP-4 to induce the accumulation of pro-MMP-9–producing cells. An intraperitoneal injection of mMCP-4 induced the accumulation of pro-MMP-9–producing cells including CD11b + Gr-1 + cells. Taken together, these data indicate that ASB17061 is a promising novel oral therapeutic agent for human AAA.