title: Macrophage-derived angiopoietin-like protein 2 accelerates development of abdominal aortic aneurysm.
abstract: 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).
  
  
  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.
  
  
  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.
authors.affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tazume
authors.forename: Keishi
authors.initials: K
authors.lastname: Miyata
authors.forename: Zhe
authors.initials: Z
authors.lastname: Tian
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Endo
authors.forename: Haruki
authors.initials: H
authors.lastname: Horiguchi
authors.forename: Otowa
authors.initials: O
authors.lastname: Takahashi
authors.forename: Eiji
authors.initials: E
authors.lastname: Horio
authors.forename: Hiroto
authors.initials: H
authors.lastname: Tsukano
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kadomatsu
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakashima
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kunitomo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Shuji
authors.initials: S
authors.lastname: Moriyama
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Ken
authors.initials: K
authors.lastname: Okamoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hara
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshinaga
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Aoki
authors.forename: Kimi
authors.initials: K
authors.lastname: Araki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hao
authors.forename: Michio
authors.initials: M
authors.lastname: Kawasuji
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
mesh_terms: D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001012:Aorta, Abdominal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D016026:Bone Marrow Transplantation; D002122:Calcium Chloride; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: C485792:ANGPTL2 protein, human; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C485793:Angptl2 protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D002122:Calcium Chloride