Macrophage-derived angiopoietin-like protein 2 accelerates development of abdominal aortic aneurysm

Autor: Zhe Tian, Motoyoshi Endo, Takashi Yoshinaga, Hiroyuki Hao, Koichi Yoshimura, Masahiko Hara, Michio Kawasuji, Otowa Takahashi, Hisashi Sakaguchi, Hiroto Tsukano, Hiroki Aoki, Haruki Horiguchi, Tsuyoshi Kadomatsu, Yuichi Oike, Eiji Horio, Ken Okamoto, Hirokazu Tazume, Shuji Moriyama, Yukiko Nakashima, Yasushi Kaneko, Keishi Miyata, Kimi Araki, Ryuji Kunitomo
Rok vydání: 2012
Předmět:
Zdroj: Arteriosclerosis, thrombosis, and vascular biology. 32(6)
ISSN: 1524-4636
Popis: 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). Methods and Results— Immunohistochemistry revealed that Angptl2 is abundantly expressed in infiltrating macrophages within the vessel wall of patients with AAA and in a CaCl 2 -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. Conclusion— 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.
Databáze: OpenAIRE