title: Increased expression of the TGF-b superfamily cytokine MIC-1/GDF15 protects ApoE(-/-) mice from the development of atherosclerosis.
abstract: OBJECTIVE
  MIC-1/GDF15 is a member of the TGF-b superfamily, which is thought to have pleiotropic roles in stress responses, inflammation, tissue injury and repair, energy homeostasis, and malignancy. MIC-1/GDF15 was recently identified as a new biomarker for the development of cardiovascular events and the outcome of atherosclerotic disease therapy. The aim of our study was to determine if MIC-1 also directly exerts pro- or antiatherogenic properties during the development of atherosclerosis.
  
  
  RESULTS
  We investigated the effect of transgenic overexpression of MIC-1 in macrophages in the ApoE(-/-) mouse model of atherosclerosis. After 6 months of high-fat diet, MIC-1/GDF15 transgenic ApoE(-/-) mice had smaller atherosclerotic lesions; however, no differences in lesion composition, pro- or anti-inflammatory cytokine production, or serum levels of lipids or cytokines were detected.
  
  
  CONCLUSIONS
  Our results suggest that MIC-1 has an overall protective effect on the disease process, but further studies will be required to define its mechanism of action.
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW 2010, Australia. heiko.johnen@gmail.com
authors.forename: Heiko
authors.initials: H
authors.lastname: Johnen
authors.forename: Tamara
authors.initials: T
authors.lastname: Kuffner
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Wu
authors.forename: Roland
authors.initials: R
authors.lastname: Stocker
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D015415:Biomarkers / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000009:adverse effects; D016207:Cytokines / Q000378:metabolism; D004036:Diet, Atherogenic / Q000009:adverse effects; D004195:Disease Models, Animal; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D002791:Cholesterol, Dietary; D016207:Cytokines; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D008055:Lipids