AT1 blockade attenuates atherosclerotic plaque destabilization accompanied by the suppression of cathepsin S activity in apoE-deficient mice
| Autor: | Masafumi Kuzuya, Kohji Sato, Kenji Okumura, Akihisa Iguchi, Xian Wu Cheng, Takeshi Sasaki, Lina Hu, Toyoaki Murohara, Kae Nakamura, Haizhen Song, Taiju Hayashi |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Apolipoprotein E medicine.medical_specialty Tetrazoles Renin-Angiotensin System Mice chemistry.chemical_compound Apolipoproteins E Internal medicine Renin–angiotensin system medicine Animals Cathepsin S Cathepsin Angiotensin II receptor type 1 Chemistry Macrophages Imidazoles Atherosclerosis Animal Feed Cathepsins Dietary Fats Angiotensin II Elastin Oxidative Stress Endocrinology Apocynin Collagen Angiotensin I Cardiology and Cardiovascular Medicine Olmesartan medicine.drug |
| Zdroj: | Atherosclerosis. 210:430-437 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/j.atherosclerosis.2009.12.031 |
| Popis: | Although it has been suggested that the renin-angiotensin (RA) system and cathepsins contribute to the development and vulnerability of atherosclerotic plaque, the interaction of the RA system and cathepsins is unclear. Thus, we investigated the effects of an angiotensin II type 1 receptor (AT1) antagonist, olmesartan, on the levels of cathepsins in brachiocephalic atherosclerotic plaque and plaque stabilization in apolipoprotein E (apoE)-deficient mice receiving a high-fat diet. Under a high fat diet, treatment with olmesartan (3 mg/kg per day) maintained collagen and elastin at high levels and attenuated the plaque development and cathepsin S (Cat S) level in the atherosclerotic plaque of apoE-deficient mice. The administration of olmesartan suppressed the accumulation of macrophages in plaque. Immunoreactivities of Cat S and AT1 were observed in macrophages. The amount of Cat S mRNA and the macrophage-mediated collagenolytic and elastolytic activities in cultured macrophages were increased by exposure to angiotensin II (Ang II), and these effects were diminished by olmesartan and the NADPH-oxidase inhibitor apocynin. These results suggested that Cat S derived from macrophages is involved in the mechanisms of atherosclerotic plaque vulnerability, and AT1 blocker maintained the plaque stabilization alongside the suppression of Cat S and macrophage activities. |
| Databáze: | OpenAIRE |
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