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Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice
Published on: September 28, 2015
Increased local angiotensin II formation in aneurysmal aorta
Masayoshi Nishimoto1, Shinji Takai, Hitoshi Fukumoto
1Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki City, Osaka 569-8686, Japan.
Angiotensin II-forming enzymes, angiotensin converting enzyme (ACE) and chymase, are significantly elevated in aortic aneurysms. This increase in enzymes may contribute to the development of aortic aneurysms.
Area of Science:
- Cardiovascular Science
- Enzymology
- Vascular Biology
Background:
- Aortic aneurysms are characterized by abnormal dilation of the aorta.
- The renin-angiotensin system plays a role in cardiovascular homeostasis.
- Angiotensin II is a key effector peptide in the renin-angiotensin system.
Purpose of the Study:
- To investigate the levels and cellular localization of angiotensin II-forming enzymes, specifically angiotensin converting enzyme (ACE) and chymase, in human aneurysmal and normal aortas.
- To determine if increased activity of these enzymes is associated with aortic aneurysm development.
Main Methods:
- Aneurysmal aortic specimens (n=14) and normal aortic specimens (n=16) were collected.
- ACE and chymase activities were measured in tissue homogenates.
- Immunohistochemistry was performed to identify the cellular distribution of ACE and chymase.
Main Results:
- ACE activity was significantly higher in aneurysmal aortas (0.82 mU/mg protein) compared to normal aortas (0.14 mU/mg protein).
- Chymase activity was markedly elevated in aneurysmal aortas (17.9 mU/mg protein) versus normal aortas (1.02 mU/mg protein).
- ACE-positive cells (macrophages) and chymase-positive cells (mast cells) were increased in the intima, media, and adventitia of aneurysmal aortas compared to normal aortas.
Conclusions:
- Both ACE and chymase, key enzymes in angiotensin II formation, are significantly increased in human aortic aneurysms.
- The enhanced presence and activity of these enzymes in specific aortic wall layers suggest a role in the pathogenesis of aortic aneurysms.
- Elevated local angiotensin II production may be a contributing factor to the development and progression of aortic aneurysms.
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