期刊
ATHEROSCLEROSIS
卷 216, 期 2, 页码 307-312出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2011.02.025
关键词
Abdominal aortic aneurysm; Angiotensin converting enzyme inhibitor; Inflammation; Cytokine; Human
资金
- KAKENHI [19390335, 20659199, 20390348, 21390367, 21390362]
- MEXT, Japan
- Kimura Memorial Heart Foundation
- Grants-in-Aid for Scientific Research [21390362, 20390348, 19390335, 20659199, 21390367] Funding Source: KAKEN
Abdominal aortic aneurysm (AAA) is characterized by the destruction of tissue architecture due to chronic inflammation of unknown etiology. Recent studies have indicated that control of inflammation is a promising therapeutic strategy; however, no established pharmacological intervention is currently available for AAA. We found that hepatocyte growth factor (HGF) was expressed in aneurysmal tissue, and colocalized with von Willebrand factor, the endothelial cell marker, in the most damaged part of the aneurysmal walls. In ex vivo cultures of human AAA tissue, exogenously added HGF in the presence of tumor necrosis factor-alpha (TNF-alpha) enhanced the secretion of anti-inflammatory cytokine interleukin-10 (IL-10) and suppressed the secretion of proinflammatory monocyte/macrophage chemotactic protein-1 (MCP-1). The angiotensin converting enzyme (ACE) inhibitors, imidaprilat and perindoprilat, enhanced the secretion of endogenous HGF, augmented the TNF-alpha-induced IL-10 secretion and suppressed MCP-1 secretion from AAA tissue. The ACE inhibitors also augmented the expression of HGF in the presence of bradykinin in human aortic endothelial cells in culture (HAECs). In contrast, HGF secretion was not affected by either an angiotensin II type 1 receptor (AT1) antagonist or angiotensin II in AAA tissue or in HAECs. These results suggested that angiotensin converting enzyme inhibitors may be useful in controlling chronic inflammation in AAA, partly due to their enhancement of HGF secretion. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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