title: Resistin is secreted from macrophages in atheromas and promotes atherosclerosis.
abstract: OBJECTIVE
  Resistin belongs to a family of cysteine-rich secreted polypeptides that are mainly produced by monocytes/macrophages in humans. Recently, high concentrations of resistin were shown to induce vascular endothelial dysfunction and vascular smooth muscle cell proliferation. We examined if resistin was secreted from macrophages locally in atheromas and if it affected vascular cell function in human.
  
  
  RESULTS
  Immunohistochemical staining of human vessels showed that aortic aneurysms exhibited resistin-positive staining areas along macrophage infiltration, while normal arteries and veins did not. Co-localization of resistin and CD68 (a marker for macrophages) was observed in immunofluorescent double staining of aneurysms. Resistin mRNA was expressed much higher in cultured monocytes/macrophages than in human vascular smooth muscle cells (VSMCs) and human umbilical venous endothelial cells (HUVECs). This suggested that the resistin in aneurysms originates from macrophages within the vessels. To determine the effects of resistin on atherosclerosis, HUVECs and human VSMCs were incubated with resistin (10-100 ng/mL for 4 approximately 24 h). In HUVECs, plasminogen activator inhibitor (PAI)-1 release was assayed by ELISA, while the PAI-1 and endothelin (ET)-1 mRNA levels were analyzed by Northern blotting. Both were increased significantly with resistin treatment by factors of 1.3-2.5 (p<0.05). Migratory activity of VSMCs measured by scratched wound assay also increased significantly (1.6 times, p<0.05). In summary, macrophages infiltrating atherosclerotic aneurysms secrete resistin, and resistin affects endothelial function and VSMC migration.
  
  
  CONCLUSIONS
  Resistin secreted from macrophages may contribute to atherogenesis by virtue of its effects on vascular endothelial cells and smooth muscle cells in humans.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, South Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Jung
authors.forename: Ki-Ho
authors.initials: KH
authors.lastname: Park
authors.forename: Young Min
authors.initials: YM
authors.lastname: Cho
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Chung
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Cho
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Cho
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Seong Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Hong Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D000199:Actins / Q000032:analysis; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017544:Aortic Aneurysm, Abdominal / Q000276:immunology* / Q000378:metabolism; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D019332:Endothelin-1 / Q000032:analysis / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D052243:Resistin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019332:Endothelin-1; D017395:Plasminogen Activator Inhibitor 1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D052243:Resistin; C067980:CD68 antigen, human; D000097382:CD68 Molecule