Increased expression of the TGF-b superfamily cytokine MIC-1/GDF15 protects ApoE(-/-) mice from the development of atherosclerosis

Cardiovasc Pathol. Nov-Dec 2012;21(6):499-505. doi: 10.1016/j.carpath.2012.02.003. Epub 2012 Mar 2.


Aim: 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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Aorta / pathology*
  • Apolipoproteins E / deficiency*
  • Atherosclerosis / chemically induced
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology*
  • Atherosclerosis / prevention & control*
  • Biomarkers / metabolism
  • Cholesterol, Dietary / adverse effects
  • Cytokines / metabolism
  • Diet, Atherogenic / adverse effects
  • Disease Models, Animal
  • Growth Differentiation Factor 15 / metabolism*
  • Lipids / blood
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout


  • Apolipoproteins E
  • Biomarkers
  • Cholesterol, Dietary
  • Cytokines
  • Gdf15 protein, mouse
  • Growth Differentiation Factor 15
  • Lipids