Format

Send to

Choose Destination
Eur J Pharmacol. 2019 Aug 5;856:172403. doi: 10.1016/j.ejphar.2019.05.032. Epub 2019 May 23.

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.

KEYWORDS:

ASB17061; Abdominal aortic aneurysm; CD11b(+)Gr-1(+); Chymase; MMP-9

PMID:
31128093
DOI:
10.1016/j.ejphar.2019.05.032
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center