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ASB17061, a novel chymase inhibitor, prevented the development of angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E-deficient mice.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2019 Aug 05; Vol. 856, pp. 172403. Date of Electronic Publication: 2019 May 23. - Publication Year :
- 2019
-
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  <superscript>+</superscript>  Gr-1  <superscript>+</superscript>  cells. Taken together, these data indicate that ASB17061 is a promising novel oral therapeutic agent for human AAA.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Aortic Aneurysm, Abdominal metabolism
Colitis prevention & control
Enzyme Precursors metabolism
Male
Matrix Metalloproteinase 9 metabolism
Mice
Mice, Inbred BALB C
Angiotensin II pharmacology
Aortic Aneurysm, Abdominal chemically induced
Aortic Aneurysm, Abdominal prevention & control
Apolipoproteins E deficiency
Benzoic Acid pharmacology
Chymases antagonists & inhibitors
Serine Proteinase Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 856
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 31128093
- Full Text :
- https://doi.org/10.1016/j.ejphar.2019.05.032