Macrophage-Derived Angiopoietin-Like Protein 2 Accelerates Development of Abdominal Aortic Aneurysm

作者：Tazume Hirokazu; Miyata Keishi; Tian Zhe; Endo Motoyoshi; Horiguchi Haruki; Takahashi Otowa; Horio Eiji; Tsukano Hiroto; Kadomatsu Tsuyoshi; Nakashima Yukiko; Kunitomo Ryuji; Kaneko Yasushi; Moriyama Shuji; Sakaguchi Hisashi; Okamoto Ken; Hara Masahiko; Yoshinaga Takashi; Yoshimura Koichi; Aoki Hiroki; Araki Kimi; Hao Hiroyuki; Kawasuji Michio; Oike Yuichi^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2012, 32(6): 1400-+.

DOI：10.1161/ATVBAHA.112.247866

• abdominal aortic aneurysm
• angiopoietin-like protein 2
• chronic inflammation
• macrophage
• matrix metalloproteinase

Objective-Recently, we reported that angiopoietin-like protein 2 (Angptl2) functions in various chronic inflammatory diseases. In the present study, we asked whether Angptl2 and its associated chronic inflammation contribute to abdominal aortic aneurysm (AAA). %26lt;br%26gt;Methods and Results-Immunohistochemistry revealed that Angptl2 is abundantly expressed in infiltrating macrophages within the vessel wall of patients with AAA and in a CaCl2-induced AAA mouse model. When Angptl2-deficient mice were used in the mouse model, they showed decreased AAA development compared with wild-type mice, as evidenced by reduction in aneurysmal size, less severe destruction of vessel structure, and lower expression of proinflammatory cytokines and matrix metalloproteinase-9. However, no difference in the number of infiltrating macrophages within the aortic aneurysmal vessel wall was observed between genotypes. AAA development was also significantly suppressed in wild-type mice that underwent Angptl2-deficient bone marrow transplantation. Expression levels of proinflammatory cytokines and metalloproteinase-9 in Angptl2-deficient macrophages were significantly decreased, and those decreases were rescued by treatment of Angptl2 deficient macrophages with exogenous Angptl2. %26lt;br%26gt;Conclusions-Macrophage-derived Angptl2 contributes to AAA development by inducing inflammation and degradation of extracellular matrix in the vessel wall, suggesting that targeting the Angptl2-induced inflammatory axis in macrophages could represent a new strategy for AAA therapy. (Arterioscler Thromb Vasc Biol 2012;32:1400-1409.)

• 出版日期2012-6